brazilian wandering spider vs rattlesnake

The World’s Most Venomous Spider: The Brazilian Wandering Spider

Published: August 10, 2023

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Few things fear people’s hearts, like the mention of venomous spiders. According to the Guinness World Records , venomous spiders are some of the most dangerous creatures on Earth, and the Brazilian Wandering Spider is the world’s most venomous spider. This elusive arachnid is found in the rainforests of South America, more specifically in Brazil, Argentina, and French Guiana. ‘

It is considered one of Brazil’s most significant public health threats, with a potent venom capable of causing extreme pain, paralysis, and even death. Despite its fearsome reputation, however, the Brazilian Wandering Spider is a fascinating and unique creature with many incredible features that make it stand out from other spiders.

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Brazilian Wandering Spider’s Habitat And Range

The Brazilian Wandering Spider is found in the rainforests of South America. These rainforests are the world’s largest and most biodiverse terrestrial ecosystems, covering an area of approximately 6.7 million square kilometers. This equates to roughly 40% of the total area of South America and spans nine countries, including Brazil, Peru, and Colombia.

The Amazon rainforest, the most extensive rainforest on Earth, plays an essential role in the Brazilian Wandering Spider’s habitat and range. The spider relies heavily on the dense canopy of trees in these rainforests for shelter and protection. The Amazon rainforest also provides the spider with an abundant prey source, including insects, small mammals, and other spiders.

The South American rainforests are characterized by their warm and humid climate, which creates the ideal conditions for the Brazilian Wandering Spider to thrive. These ecosystems also have a high rainfall throughout the year, which sustains the dense vegetation and creates an ideal environment for spiders to hunt and reproduce.

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Specific Locations The Brazilian Wandering Spider Is found

The Brazilian Wandering Spider is most commonly found in Brazil. It can also be found in other parts of South America, such as Argentina and French Guiana. In Brazil, the spider can be found in various regions. This includes the Amazon rainforest, the Atlantic forest, and the Caatinga ecosystem.

The Atlantic forest, a tropical forest that spans the Brazilian coast, is also an important habitat for the Brazilian Wandering Spider. This ecosystem is under threat due to deforestation and urbanization. This has resulted in the loss of the spider’s natural habitat.

In French Guiana, the spider is present in the Guiana Amazonian Park, a protected area of the Amazon rainforest managed by the French government. The Guiana Amazonian Park is home to an array of biodiversity, including monkeys, jaguars, and over 400 species of birds. This makes it an important region for the Brazilian Wandering Spider’s survival.

Brazilian Wandering Spider’s Characteristics

It is a remarkable arachnid species found in the rainforests of South America. It has numerous unique characteristics from other spiders. The Spider is large and intimidating, measuring up to 10 inches (25 cm) in leg span. Its body size ranges from 0.98 to 1.77 inches (2.5 to 4.5 cm) in length. This makes it one of the biggest spider species in the world. It has eight long and hairy legs, which help it move quickly and climb trees effortlessly.

The spider is striking, with a shiny brown or black body covered in short fine hairs. Its legs are also covered in fine hairs with dark stripes or spots. These markings have a unique pattern that helps to identify the spider from other species. Unlike most spiders, the Brazilian Wandering Spider doesn’t have a distinct web-spinning organ. But instead moves around the forest floor and trees in search of its prey.

Behavioral Patterns

They are aptly named because they are known to wander about and can cover a great distance while searching for food and mates. It’s primarily active at night and is a solitary hunter that preys on insects, spiders, rodents, and even small snakes. It has a unique hunting technique where it grabs its prey with its front legs and sinks fangs into it, injecting a potent venom that can quickly immobilize and kill its victim. Interestingly, this spider can adjust the amount of venom it injects to fit the size and the species of its prey, a skill unique to this spider species.

During the mating season, the Brazilian Wandering Spider’s behavior changes drastically. The males will approach females cautiously, tapping on the female’s web to signal their interest. They then perform a complex courtship display that involves waving their front legs, drumming their pedipalps, and vibrating on webs. The more intricate the display, the higher the chances of mating with the female.

Brazilian Wandering Spider’s Venom

The venom of the Brazilian Wandering Spider is considered one of the deadliest in the world. The potency of the venom is due to the presence of a potent neurotoxin called PhTx3. This toxin is responsible for the spider’s ability to paralyze its prey and defend itself from predators.

In scientific studies, the venom of the Brazilian Wandering Spider has proven to be significantly more toxic than other venomous spiders, such as the Black Widow and the Brown Recluse. The effectiveness of this venom is a result of its unique chemical structure, which allows it to attack the nervous system of its victim and cause significant damage.

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Effects Of Venom On Humans And Animals

The effects of the venom of the Brazilian Wandering Spider can be devastating. When bitten, victims may experience severe pain, muscle spasms, and even paralysis. In extreme cases, the venom can cause respiratory failure, resulting in death.

While the venom initially causes pain and discomfort, it can lead to severe, long-lasting symptoms. In addition to causing physical harm, the venom can also have psychological effects, leading to anxiety, panic attacks, and even PTSD.

Animals are also susceptible to the venom of the Brazilian Wandering Spider . Small animals, such as mice and birds, are often preyed upon by the spider, while larger animals, such as dogs and cats, can be bitten accidentally.

Public Health Threat And Prevention

The Brazilian Wandering Spider is a significant public health threat in Brazil, with hundreds of bites reported yearly. The spider has a wide distribution throughout the country, and its venom is particularly toxic, making it a serious risk to human health.

Also, the spider is especially dangerous because it is highly aggressive and can be found in homes, gardens, and public spaces. This means that anyone can encounter the spider, regardless of location or occupation, making it difficult to prevent bites.

Measures Taken To Prevent Bites And Treat Victims

To prevent bites from the Brazilian Wandering Spider, it is essential to take steps to reduce the risk of encountering the spider. This may include keeping homes and gardens free of clutter and debris, sealing windows and doors, and avoiding areas where the spider is known to live.

In the case of a bite, it is important to seek medical attention immediately. While no anti-venom is available, medical professionals can offer supportive care to alleviate symptoms and prevent complications.

Frequently Asked Questions

The Brazilian Wandering Spider’s venom contains a potent neurotoxin called PhTx3, which can cause extreme pain, muscle spasms, and paralysis in humans. This venom is 20 times more deadly than a rattlesnake’s and can cause respiratory failure in victims.

It is primarily found in South and Central America, especially in the Amazon rainforest. They hide in dark, moist environments such as piles of leaves, tree trunks, and burrows.

To avoid contact with the Brazilian Wandering Spider, it is important to inspect your surroundings, especially before putting on shoes or reaching into piles of debris. It is advisable to wear gloves and long sleeves when working outdoors or in areas where these spiders may be present. If you suspect a Brazilian Wandering Spider has bitten you, seek medical attention immediately.

Overall, the Brazilian Wandering Spider is a fascinating and deadly spider that deserves respect and caution. Though its venom is incredibly potent, the spider itself is a remarkable creature. Its ability to move quickly and seamlessly across the ground makes it a formidable predator in its native habitats. 

Despite its fearsome reputation, we must learn to coexist with this remarkable arachnid, preserving its unique place in the natural world. Given the immense diversity and beauty of our planet’s biodiversity, the Brazilian Wandering Spider reminds us that we still have much to learn about the remarkable creatures that share our planet.

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Fact Animal

Facts About Animals

Brazilian Wandering Spider Facts

Brazilian wandering spider profile.

There are more than 50,000 species of spider, and the vast majority are less dangerous than a honeybee. Almost none are aggressive, and of those with medically significant venom, only a small percentage are capable of causing death. So, on the whole, arachnophobes are just being a bit silly.

But there’s one spider that vindicates all of these fears, and few animals are as globally renowned to be a serious threat to human lives as the Brazilian Wandering Spider .

Brazilian Wandering Spiders are actually 9 species of spider in the same genus ‘Phoneutria’, one of which is found in Central America, with the rest in South America.

Brazilian Wandering Spider Facts Overview

These spiders are called wandering spiders because of instead of spinning a web to wait for food, or occupying a lair, they spend their night wandering in the leaf litter of the jungle floor for prey.

The sensitive hairs on its body help detect vibrations of passing prey, and it will feed on insects, lizards, frogs and any animals as large as itself.

During the day they will hide under logs, rocks, or inside termite mounds and banana plants. They will also sometimes wander into urban areas and homes, where they can come into contact with humans.

Brazilian wandering spiders are aggressive , dangerous and frightening. For once, this is an animal you should be wary of.

The females are larger, around 50% heavier than males, and produce more venom, and this might be a clue as to why their Greek name translates to “ Mudress” . These spiders will often stand and fight and have an intimidating threat display.

The potency of their venom is one of the reasons they’re so dangerous, and their ability to hide away in fruit and shoes explains why most bites are on extremities.

Interesting Brazilian Wandering Spider Facts

1. armed spiders.

In Brazilian, these are sometimes known as armed spiders, on account of their elongated front legs.

They can convey quite a bit of information with these legs, and as wandering spiders, use them to get about the forest, looking for food.

2. Banana Spiders

They’re also sometimes called ‘banana spiders’ on account of their status as a stowaway on popular fruit imported from the tropics.

This is becoming less common as stricter regulations ensure there’s less contamination of fruits, but there’s always a chance your next bunch of bananas will have a family of these spiders living inside it.

3. They have the largest venom glands of any spider

Females produce more venom than males, but both sexes have enormous venom glands. These glands are even more impressive when you consider the size of the spider is significantly less than the largest around.

The venom glands of the Brazilian Wandering Spider are over a centimetre long, and this is all housed inside the bright red chelicerae (mouth parts) which they are quick to display whenever they get upset. 1

4. They’re aggressive

These spiders can grow quite large and have long, brightly-coloured legs. Unlike most spiders, they’re known to stand their ground when threatened and are far quicker to bite than many other species.

They’ll still try to scurry away where possible, and they’re not out to get anybody.

But where most other species will flee, the wandering spiders’ aggression does make it more likely to be involved in incidents.

Most bites are on fingers and toes, a sign that they’re being stepped on or grabbed inadvertently. When the spider feels cornered, it’ll rear up on its back legs and waves its colourful arms around as a warning.

Then it’ll sway side to side, beckoning you to have a go. Anything foolhardy enough to call this bluff gets a wealth of envenomation effects. 2 3

5. They give some men erections

There are ways to accomplish this with fewer side effects, but a bit from a Brazilian wandering spider does come with a certain Viagral quality.

This isn’t as fun as it might sound. Prolonged erections in this manner are likely to harm and destroy muscles and blood vessels in the penis and could cause irreparable damage.

Besides this, the assault on the central nervous system that comes with envenomation by this spider doesn’t sound worth it. 4

6. And some people die

This assault brings with it a whole host of unpleasant symptoms. Seizures, foaming at the mouth, inability to speak, collapse, and a host of other miserable experiences.

Paralysis is possible, as is cardiac shock. Blood vessels can burst in the brain, or anywhere else, and in many cases, this can be enough to kill a person.

This spider has one of the most potent venoms of all, and there are multiple legitimate records of death as a result of bites.

7. But they’re rarely fatal

While the Brazilian wandering spider is potentially one of the most dangerous spiders in the world, there is some evidence to suggest it gives a dry bite, defensively.

This means that despite exceptionally toxic venom, the amount actually injected is less than some of the other contenders, and this is what makes it typically less lethal than the Australian funnel webs.

These spiders are classified as Dangerous Wild Animals and would therefore require a special permit to keep. Bites from wandering spiders are common in South America, but antivenom is often readily available, and they rarely result in death.

In most cases, lethal bites are cases of a very young or very old victim, and few people of healthy age are killed. 5

8. They do invade the UK sometimes

These unquestionably scary spiders show up in supermarkets in the UK on occasion, having hitched a ride on banana shipments.

On more than one occasion they’ve made their way into shoppers’ homes, but it doesn’t appear that there are any cases of them biting people as a result.

These spiders aren’t suited for temperate climates and don’t survive Winter, so there’s no risk of them multiplying.

Brazilian Wandering Spider Fact-File Summary

Scientific classification, fact sources & references.

• PeerJ. (2017), “ Dimensions of venom gland of largest venom glands in all spiders ”, Bio Numbers.
• Dave Clarke (2010), “ Venomous spider found in Waitrose shopping ‘beautiful but aggressive’” , The Guardian.
• “ Phoneutria Perty (Arachnida: Araneae: Ctenidae) ”, UF-IFAS University of Florida
• Kátia R.M. Leite (2012), “ Phoneutria nigriventer spider toxin Tx2-6 causes priapism and death: A histopathological investigation in mice ”, Science Direct.
• “ Brazilian wandering spiders: Bites & other facts ”, Live Science.

Brazilian Wandering Spider

The Brazilian Wandering Spider (Phoneutria fera) is a teardrop-shaped arachnid with a brown coloration. Known for its potent venom, it thrives in both the lush rainforests and human dwellings of Brazil. Its notorious wandering behavior makes it a significant presence in its habitats.

Fascinating Facts about Brazilian Wandering Spider

Here are 3 interesting facts about Brazilian Wandering Spider:

• The Brazilian Wandering Spider is considered the world's most venomous spider by the Guinness World Records.
• They are known as 'wandering' spiders because they roam the jungle floor at night instead of residing in a lair or web.
• Despite their notorious reputation, their bites rarely cause death in humans due to the small amount of venom they inject.

Taxonomy and Classification

Here is the scientific categorization of Brazilian Wandering Spider, providing a glimpse of their position in the biological hierarchy:

Lifecycle and Growth

Brazilian Wandering Spider's life is a journey of transformation - an adventure marked by the following captivating stages:

Egg → Spiderling → Adult

The Brazilian Wandering Spider, primarily found in the rainforest, exhibits a lifecycle that spans both wilderness and human habitats. From egg to adult, it navigates a complex path through dense foliage and human dwellings, adapting to these contrasting environments.

Brazilian Wandering Spider Behaviour and Adaptations

Brazilian Wandering Spiders are known for their nomadic behavior. Instead of building webs to catch prey, they actively hunt at night, using their highly developed senses, particularly vision, to locate and stalk their prey.

These arachnids have adapted to a wide range of habitats, from forests to urban areas. Their potent neurotoxic venom, one of the most powerful among spiders, allows them to incapacitate and consume a variety of prey.

Brazilian Wandering Spider Interaction with the Ecosystem

Now, let's look at how they help maintain the balance in the ecosystem:

• Brazilian Wandering Spiders play a crucial role in controlling the population of their prey, which includes insects and small mammals.
• They serve as a food source for larger animals, contributing to the food chain in their ecosystem.
• Their venom, although dangerous to humans, is studied for medicinal purposes including treatments for erectile dysfunction and pain relief.

Threats to Brazilian Wandering Spider

Despite their popularity and predator status, Brazilian Wandering Spider encounter several threats as well:

• Destruction of natural habitat due to deforestation
• Increased usage of pesticides affecting their food chain
• Climate change potentially disrupting their breeding patterns

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Brazilian Wandering Spider

The Brazilian Wandering Spider (Phoneutria fera) is an aggressive and highly venomous spider . It was first discovered in Brazil hence its name. However, this genus is known to exist elsewhere in South and Central America .

The Brazilian Wandering spider is a member of the Ctenidae family of wandering spiders.

The Brazilian Wandering spider appeared in the Guinness Book of World Records 2007 for being the most venomous animal .

In this particular genus, there are five known similar species whose members are also highly venomous. They include some of the relatively few species of spiders that present a threat to human beings.

Brazilian Wandering Spider Characteristics

The Brazilian wandering spider can grow to have a leg span of up to 4 – 5 inches. They are large hairy spindly-looking spiders who have eight eyes, two of which are large. Brazilian wandering spiders are fast-moving spiders, their legs are strong and spiny and they have distinctive red jaws which they display when angered.

The Brazilian wandering spider is not a Tarantula . Brazilian wandering spiders are not even in the same family group. Tarantulas are harmless to humans and are mostly ambush killers who wait for prey to come to them. Brazilian wandering spiders are active hunters. Brazilian wandering spiders and Tarantulas do have one thing in common, however, they do not eat bananas.

Brazilian Wandering Spider Habitat and Spider Webs

The Brazilian Wandering spider is so-called because it wanders the jungle floor, rather than residing in a lair or maintaining a web. This is another reason it is considered so dangerous. In densely populated areas, the Brazilian Wandering spider will usually search for cover and dark places to hide during daytime, leading it to hide within houses, clothes, cars, boots, boxes and log piles. This usually causes accidents when people disturb them.

The Brazilian Wandering spider is also called the ‘banana spider’ as it is occasionally found within shipments of bananas. As a result, any large spider appearing in a bunch of bananas should be treated with due care.

Brazilian Wandering Spider Diet

Adult Brazilian Wandering spiders eat crickets, other large insects, small lizards and mice. Spiderlings of this species eat flightless fruit flies and pinhead crickets.

Brazilian Wandering Spider Reproduction

All spiders produce silk, a thin, strong protein strand extruded by the spider from spinnerets most commonly found on the end of the abdomen. Many species use it to trap insects in webs, although there are many species that hunt freely such as the Brazilian Wandering spider. Silk can be used to aid in climbing, form smooth walls for burrows, build egg sacs, wrap prey and temporarily hold sperm, among other applications.

Brazilian Wandering spiders reproduce by means of eggs, which are packed into silk bundles called egg sacs. The male spider must (in most cases) make a timely departure after mating to escape before the females normal predatory instincts return.

Mature male spiders have swollen bulbs on the end of their palps for this purpose and this is a useful way to identify whether the spider is male or female. Once the sperm is inside the female spider, she stores it in a chamber and only uses it during the egg-laying process, when the eggs come into contact with the male sperm for the first time and are fertilized. The Brazilian Wandering spiders life cycle is 1 – 2 years.

Brazilian Wandering Spider Venom

Bites from the Brazilian Wandering spider may result in only a couple of painful pinpricks to full-blown envenomed. In either case, people bitten by this spider or any Ctenid should seek immediate emergency treatment as the venom is possibly life threatening.

The Phoneutria fera and Phoneutria nigriventer (two species of wandering spider) are the two most commonly implicated as the most vicious and deadly of the Phoneutria spiders.

The Phoneutria not only has a potent neurotoxin, but is reported to have one of the most excruciatingly painful envenoms of all spiders due to its high concentration of serotonin. They have the most active venom of any living spiders.

One of their members, the Brazilian Huntsman, is thought to be the most venomous spider in the world. Brazilian wandering spiders are certainly dangerous and bite more people than any other spiders.

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I've always been passionate about animals which led me to a career in training and behaviour. As an animal professional I'm committed to improving relationships between people and animals to bring them more happiness.

Which is the world’s deadliest spider, really?

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It seems Ebola and terrorism may have lost their scare factor. That is because journalists have once again turned to arachnophobia . “Brazilian Wandering spider found under a bunch of bananas in Waitrose home delivery,” said one newspaper recently.

Every few months, almost like clockwork, a media hype about these arachnids surfaces in the press. But we rarely find a balanced story about deadly spiders. Just how toxic are they, really?

Trying to compare spider toxicities is like comparing apples and doorknobs. There are different levels of effects, some painful, others not so much. Probably the most reasonable way to compare would be to look at historic fatalities.

The most commonly reported group is the wandering spiders of the genus Phoneutria . These are traditionally the darlings of the media banana spider reports. Always listed as deadly but are they really?

A study in 2000 , described 422 bites by Phoneutria spiders (pictured above), mostly P. nigriventer and P. keyserlingi in eastern coastal Brazil. Two children were seriously ill as a result of the bites – one died. However, more than 80% of the remaining bite victims had mild or no symptoms.

Another frequently cited dangerous species is P. fera , however, this spider lives in the Amazon, far from the banana growing areas in Brazil – and most of the people. And although Brazil produces large quantities of the fruit, most are eaten domestically so little exportation occurs.

Then there is the fact that most of the bananas shipped to North America originate from Central America and northwestern South America, far from areas containing large Phoneutria spiders. So these spiders pose little threat outside of Brazil (but there can be exceptional cases such as the one reported in the British supermarket Waitrose).

Of all the spiders whose toxicity is currently known, probably the most toxic are the funnel-web spiders of Australia (of the genera Atrax and Hadronyche ). Their bites are lethal to small children within minutes or hours and adults within 24 hours – but, having said this, there have been no Australian fatalities since anti-venom was developed.

Widow spiders of the genus Latrodectus cause a fair bit of morbidity. However, death from widow bite is pretty much a thing of the past as supportive care and anti-venom has provided tremendous relief. One mitigating factor is that deaths during the early part of the 20th century may have been due to bites that occurred in men in outhouses bitten on dangling genitalia where thin skin and heavy vasculisation allowed for quick introduction of venom. Indoor plumbing has minimised widow bites.

“Brown recluse and related spiders of the genus Loxosceles have a widespread reputation for causing damage, but, like Phoneutria spiders, there is a great deal of exaggeration. Most recluse bites cause only minor problems. About 10% develop significant skin necrosis but even so, loxoscelism experts recommend these can be treated with minimal intervention. Fewer than than 1% of recluse bites become systemic, typically in children, and can cause death in 12 to 30 hours. However, dialysis and hydration can reverse the systemic effects.

The media likes to stir up anxiety using toxic spiders in attempts to attract an audience. However, for most of us, spiders are less of a threat than driving.

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11 deadliest spiders

From the funnel web spider to the brown recluse, here are some of the deadliest spiders on Earth.

Spiders are some of the most successful arthropods on the planet, having colonized every continent except Antarctica. Not all of these eight-legged arachnids are venomous, but some can be deadly to humans . From the notorious black widow to the ultra-deadly funnel web spider, here are some of the deadliest spiders on Earth.

Brown recluse spider

As their name suggests, brown recluse spiders ( Loxosceles reclusa ) have a shy nature and tend to hide away in dark, sheltered places. However, the brown recluse spider will bite if they feel threatened, and their bites can be deadly. They are usually found in the south and central United States, spanning southeastern Nebraska to southwestern Ohio, south to northwestern Georgia and into Texas.

The brown recluse spider can be dangerous to people because their venom contains a toxin that can cause skin necrosis (rotting). For the most part, symptoms, such as burning and itching at the bite site, as well as fever and nausea, develop a few hours after a bite. In extreme cases, the venom can lead to serious reactions or even death, especially to more vulnerable groups such as young children and the elderly.

Hobo spider

Part of the family of spiders known as the funnel web spiders, the hobo spider ( Eratigena agrestis , formerly Tegenaria agrestis ) can be recognized by it's light to medium brown coloring and the multiple chevron patterns (v-shaped) on its abdomen pointing toward their head. They are often confused with the brown recluse spider (and vice versa), but the brown recluse is much more dangerous to humans. While hobo spiders have been known to bite if they feel threatened, there is much debate about how venomous they actually are. So much so that the Center for Disease Control and Prevention has removed them from their venomous spiders list. However, it's still wise to be cautious as hobo spider bites result in swelling and redness around the area, and can have more severe effects in young children.

Hobo spiders are not great climbers, so you'll find their funnel-shaped webs at ground level. Geographically, they can be found in western North America, in the Pacific Northwest and Great Basin, as well as distributed throughout Europe to Central Asia.

Black widow spider

In the genus Latrodectus , the black widow is one of the most venomous spiders and is found on every continent except Antarctica. In North America, they're commonly found in southern Canada and in the northeastern United States. You can identify the female black widow spider by its shiny black body and distinct red hourglass-shape on the underside of the abdomen. The male black widow is smaller in size, brown or gray in color with small red sports and does not have the hourglass marking.

While both male and female black widows are venomous, only the female is dangerous to humans. The venom of a black widow is reported to be 15 times stronger than that of a rattlesnake, although they don’t deliver as much venom in their bite, so fatalities are rare. That’s not to say a black widow bite isn’t painful! Those unlucky enough to be bitten by a black widow will experience nausea, fever, sweating, restlessness, muscle cramps and labored breathing, and these symptoms may last for several days.

Brazilian wandering spider

Commonly referred to as armed spiders or banana spiders (as they tend to be found hiding within shipments of bananas), the Brazilian wandering spider is one that you'll definitely want to avoid. They belong to the genus Phoneutria , Greek for "murderess," which is quite apt as they are one of the most venomous spiders on Earth.

This arachnid is aggressive, and rather than camping out, the Brazilian wandering spider actively hunts its prey, searching the jungle floor at night. If you ever find yourself in Central and South America, such as Costa Rica or Argentina, watch out! Their neurotoxic venom is extremely painful and affects the nervous system, causing increased sweating and drooling, loss of muscle control, breathing problems, and, in some cases, unwanted prolonged erections.

Yellow sac spider

The yellow sac spiders ( Cheiracanthium) are in the family Cheiracanthiidae and they probably account for more human bites that any other type of spider. These arachnids are distributed all over the globe, from America to Northern Europe, South Africa to India, and even Australia and Japan. They’re nocturnal predators and during the day they hide in small white web cocoons.

Mildly venomous to humans, the yellow sac spider bite can be painful and sometimes misdiagnosed as brown recluse bites. Their venom can cause necrotic legions, as well as redness, swelling and sores around the bite site.

Brown widow spider

Latrodectus geometricus is the scientific name for the brown widow spider. It looks similar to its infamous " cousin " the black widow, right down to the hourglass-shaped marking on its abdomen, but there are some key differences. The brown widow’s marking is orange and yellow rather than red, and as their name suggests, they predominantly have tan and brown mottling and a spiky, rather than smooth, appearance. Believed to originate in South America, the brown widow spider is found all around the world.

The brown widow's venom is less toxic than that of its black cousin. However, it can still be deadly. Although they don't deliver as much venom as a black widow, the brown widow's bite can still cause latrodectism due to its neurotoxic venom. Symptoms of lactrodectism include pain, perspiration, muscle rigidity and vomiting.

Red widow spider

Living mostly in sand dunes in Central and Southern Florida, the red widow spider ( Latrodectus bishop) is another member of the notorious "widow" family. Their venom is just as lethal as brown and black widows, but as they live so far from human contact there has been no recorded bite in medical literature. The female red widow spider's venom is a neurotoxin which is thought to cause prolonged muscle spasms.

The red widow spider has a red-orange head and legs and a black abdomen with yellow rings around red dots. Rather than an hourglass marking like its "cousins," the red widow usually has one or two red marks.

Redback spider

Due to its strikingly similar appearance, the redback spider ( Latrodectus hasselti ) was once thought to be a sub species of the black widow spider, but it is a distinct species. Also known as the Australian black widow, you can find this creepy crawly throughout Australia, Southeast Asia and New Zealand. The redback spider has even been found in Japan, the United Arab Emirates and Belgium due to inadvertent introductions.

Highly venomous, the bite from the female redback spider can be life-threatening. Using its fangs, it injects a complex venom that causes intense pain at the bite area, in addition to sweating and goosebumps. As time goes on, these symptoms worsen and there may also be redness and swelling, as well as nausea, muscle twitching, headache and fever. Respiratory failure may occur in severe cases. Thankfully, in 1956 scientists released a redback spider antivenom which is very effective, even when used several weeks after the initial bite. No deaths have been reported since.

Funnel-web spiders

Normally in the world of spiders it is the female that is more deadly, but for funnel-web spiders ( Atrax ) the male has the more toxic bite. Any attack must be treated quickly with antivenom, especially if a child has been bitten. There have been several recorded fatalities due to the venomous bites of the funnel-web spider, with death occurring within the hour after being bitten. However, since the development of the antivenom in 1981, there haven’t been any more recorded deaths. Predominantly located in southeast Australia (Sydney), funnel-web spiders are also found in New Zealand, Chile and Europe.

Interestingly, animals such as cats and dogs can actually survive a funnel web bite – it takes about 30 minutes for their body to neutralize the toxin – it's just humans who have such a severe reaction. This venom effects the nervous system and causes symptoms such as an elevated heart rate, numbness/tingling of the mouth and difficulty breathing.

Six-eyed sand spider

Found in deserts in southern Africa, the six-eyed sand spider ( Hexophthalma hahni ) buries itself in the sand to ambush unsuspecting prey. The small, stiff hairs that cover the spider helps to hold sand particles in place, adding to its camouflage. It's otherwise known as the six-eyed crab spider due to its crab-like legs.

Another arachnid that produces venom with necrotic effects, the six-eyed sand spider is the most venomous of any of its arachnid relatives, toxicology studies reveal. Scientists have found that there are proteins within their venom that can cause tissue destruction, blood vessel leakage, and thinning of the blood. No antivenom currently exists.

Mouse spider

Black in color with stocky, thick legs and a distinctively bulbous head and jaw regions, the mouse spider ( Missulena ) looks a lot more frightening than its name sounds. One species is located in Chile, another in South America and the rest distributed throughout Australia. They live in soil-covered burrows, popping out the hinged trapdoor top to attack prey.

Their hard, large fangs can cause a deep and very painful bite. However, while scientists believe that the venom of the mouse spider is very toxic, it is rarely injected. As so few cases have been reported, it is thought that mouse spiders don't use a lot of venom or may even "dry bite." Fortunately, funnel-web spider antivenom has proven effective in cases of mouse spider bite.

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Christina is a freelancer writer and editor from the UK. She has a degree in English Language and Literature with geography from the University of Keele, and a Masters in Publishing from Anglia Ruskin University. She covers everything from Lego sets and science kits through to laptops for students. If it helps you learn, she'll help you find it for cheaper.

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What Is The Most Venomous Spider In The World?

There are tens of thousands of species of spiders crawling around this planet , and practically all of them are venomous . However, only about 25 to 30 of these are considered potentially dangerous to humans . And of these contenders, the Sydney funnel-web spider ( Atrax robustus ) reigns supreme as the most venomous (as defined by its toxicity to humans). Discover why this Eastern Australian arthropod packs such a potent bite, and how it compares to other top contenders. Venomous creatures inject their prey with damaging toxins for the purposes of hunting or self-defense, whereas something that is poisonous is passively harmful to other beings when it is consumed, or otherwise contacted.

The Funnel-Web Spider: A Closer Look

The name "funnel-web spider" corresponds to 35 species within three genera: Hadronyche, Illawarra, and Atrax – all of which build distinctive burrows/traps that feature a funnel-shaped opening, complete with trip-wires to detect prey (i.e., mostly insects, but also small lizards or frogs).

The full taxonomy for the Sydney funnel-web spider is as follows:

• Kingdom: Animalia
• Phylum: Arthropoda
• Subphylum: Chelicerata
• Class: Arachnida
• Order: Araneae
• Infraorder: Mygalomorphae
• Family: Atracidae
• Genus: Atrax
• Species: A. robustus

Found throughout the bushlands and suburban gardens of New South Wales (particularly in the greater Sydney area), this dark-colored (black or brown) critter has a glossy carapace, and generally grows up to 2 inches (5 centimeters), legs included. Upon closer inspection of its front side, daunting, rearward-facing fangs capable of puncturing human skin (and even fingernails) become apparent, as well as robust fang bases. Though the females are the larger sex, they are mostly passive, and remain in their elaborate burrows for nearly their entire lives. Males, on the other hand, are the adventurers and the aggressors.

Under the cover of darkness (funnel-web spiders are highly sensitive to light), and especially in the wake of a summer rain, mature males (i.e. two to three years old) will wander out of their burrows in search of a female. If successful, the lovers will first engage in a duel, before rising onto their hind legs and pressing their bodies together. Once copulation has occurred, males usually die within a few months, whereas the females can live for several years. It is on nights that male funnel-webs fail to locate a receptive female that they seek shelter in people's homes, and even inside their shoes. This is when bites can occur. If threatened, they may assume the same mating posture, which makes them look bigger, and flashes their fangs in the process. Males can also deploy startling agility.

The venom injected by Sydney funnel-web spiders contains a neurotoxic polypeptide called atracotoxin. This agent can wreak havoc on a primate's nervous systems, but curiously, not other mammals. It works by shorting out specific synapses. As a result, nerves fire constantly, but cannot relax, leading to a rapid heart rate, elevated blood pressure, difficulty breathing, double vision, vomiting, and numbness around the mouth (the list goes on). According to Guinness World Records , a dose of just 0.2 mg/kg of the male's venom is enough to kill a human. The venom from females, however, is four-to-six times less potent. If bitten by a male, untreated infants can succumb within 15 minutes, children within hours, and adults within a few days. There have been 13 deaths on record attributed to male Sydney funnel-web spiders.

Thankfully, the advent of antivenom has essentially eliminated human deaths at the hands (or rather, fangs) of Sydney funnel-web spiders. Despite Australia's notorious reputation, not a single fatality has occurred because of venomous spiders since the 1980s. Using robust gardening gloves, wearing thick-soled shoes (if shaken out first), and immediately (but calmly) seeking medical attention when bitten have proven to be an effective trifecta. But what about our beloved pets? Amazingly, cats and dogs naturally neutralize the toxins from funnel web spiders in about half an hour.

Comparing Venomous Contenders

Many spiders are capable of delivering a veritable witch's brew in an act of self-defense, or to unsuspecting prey. These fluids are composed of a wide range of peptides and proteins that are developed by salivary glands and administered by the fangs. In humans, some of these venoms either impact the nervous system (i.e., neurotoxins), or the tissue (cytotoxins). Along with the Sydney funnel-web, other highly-venomous (and therefore, potentially dangerous) spiders to be aware of include the redbacks and black widows (of the Latrodectus genus) , the brown recluse ( Loxosceles ), and wandering spiders ( Phoneutria ).

The redback spider ( Latrodectus hasselti ) also lurks about the Australian continent . It is the only other species of arachnid in the region responsible for killing human beings (though this has never happened since the antivenom was distributed back in 1956). Nonetheless, somewhere around 2,000 people are bitten each year, leading to intense pain, sweating, and nausea/fever.

The Brazilian wandering spider ( Phoneutria nigriventer and Phoneutria keyserlingi ) may not be the most venomous, but its bite is certainly one of the most painful. Between 1970 and 1980, just in Southeastern Brazil (it is found throughout Northern South America and parts of Central America), over 7,000 people were admitted to the hospital because of bites attributed to the "banana" spider (so named because of its propensity for hiding in shipments of the flavorful fruit). Nowadays, about 4,000 bites are reported each year in Brazil, but a small fraction of victims are injected with enough venom to require antivenom. With that said, extreme pain can be felt around the bite mark. Other symptoms include difficulty breathing, loss of muscle control, and, oddly enough, prolonged (and painful) erections in males.

The notorious black widow spider can be found in temperate regions all around the world, but is one of the few stateside spiders that causes alarm. While its venom is reported to be 15 times more potent than a rattlesnake's, unless bite victims already have a compromised immune or cardiovascular system, serious harm is rare. Instead, it is male black widows who must be on their guard, for the females sometimes kill and eat their former mate (which is where the species' common name comes from).

Brown recluse spiders ( Loxosceles reclusa ) are another highly-venomous species found in the United States (but only the South-Central portion). While its venom is capable of causing necrosis (rotting lesions), about 90% of bites do not require medical treatment (though medical attention should always be sought if you think you've been bitten).

Myths vs Reality

The biggest myth in regards to venomous spiders is simply that they are more dangerous than they actually are. First of all, spiders tend to be reclusive and passive, and would prefer not to interact with humans at all, let alone attack. Spiders focus their aggressive behaviors on things they can actually eat (namely, insects). Secondly, even if they do decide to bite a human, oftentimes, their fangs are not substantial enough to pierce the skin (though children are more susceptible than adults). Even if a spider does break the skin, it is unlikely to release a harmful dose of venom, if any at all (i.e., a dry bite). It requires both time and energy to manufacture venom, and they need this weapon for hunting and defense. Spiders are reluctant to waste this valuable resource. And finally, if all of these previous scenarios play out poorly, antivenoms are widely available in many parts of the world. Isolated and/or developing areas continue to be the exception and where a few fatalities tend to occur.

Another myth about venomous spiders is that bites always require antivenom. For many of the reasons just mentioned, medical intervention is only required in a fraction of cases. Antivenom, like many medicines, can have undesirable side effects, so it is better to take a targeted approach.

The Sydney funnel-web spider is the world's most-venomous spider and an intimidating-looking creature to boot. But with that said, there is no need to cancel your dream vacation to Australia. These spiders, like most wild animals, simply want to be left alone. Funnel-web spiders, in particular, rarely even leave their home. Understanding their preferred habitat and taking simple precautions when wading into these domains has proven to be a sufficient precaution.

In the off-chance that an unsuspecting person, having accidentally stumbled across a male specimen, is bitten, local hospitals can provide efficacious treatments. So, while funnel-web spiders may not be the most popular suburban neighbors, they still serve an important ecological role, and should be respected for it. Spiders eat other unwanted insects and provide a source of food for animals higher up the food chain. What a tangled and beautiful web we all live in.

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Holistic profiling of the venom from the Brazilian wandering spider Phoneutria nigriventer by combining high-throughput ion channel screens with venomics

F. c. cardoso.

1 Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia

2 Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Australia

A. A. Walker

M. v. gomez.

3 Department of Neurotransmitters, Institute of Education and Research, Santa Casa, Belo Horizonte, Brazil

Rodrigo Ligabue-Braun , Federal University of Health Sciences of Porto Alegre, Brazil

Luiza Gremski , Federal University of Paraná, Brazil

Associated Data

The datasets presented in this study can be found in online repositories. The name of the repository and accession number are ProteomeXchange PRIDE repository; PXD037904.

Introduction: Spider venoms are a unique source of bioactive peptides, many of which display remarkable biological stability and neuroactivity. Phoneutria nigriventer , often referred to as the Brazilian wandering spider, banana spider or “armed” spider, is endemic to South America and amongst the most dangerous venomous spiders in the world. There are 4,000 envenomation accidents with P. nigriventer each year in Brazil, which can lead to symptoms including priapism, hypertension, blurred vision, sweating, and vomiting. In addition to its clinical relevance, P. nigriventer venom contains peptides that provide therapeutic effects in a range of disease models.

Methods: In this study, we explored the neuroactivity and molecular diversity of P. nigriventer venom using fractionation-guided high-throughput cellular assays coupled to proteomics and multi-pharmacology activity to broaden the knowledge about this venom and its therapeutic potential and provide a proof-of-concept for an investigative pipeline to study spider-venom derived neuroactive peptides. We coupled proteomics with ion channel assays using a neuroblastoma cell line to identify venom compounds that modulate the activity of voltage-gated sodium and calcium channels, as well as the nicotinic acetylcholine receptor.

Results: Our data revealed that P. nigriventer venom is highly complex compared to other neurotoxin-rich venoms and contains potent modulators of voltage-gated ion channels which were classified into four families of neuroactive peptides based on their activity and structures. In addition to the reported P. nigriventer neuroactive peptides, we identified at least 27 novel cysteine-rich venom peptides for which their activity and molecular target remains to be determined.

Discussion: Our findings provide a platform for studying the bioactivity of known and novel neuroactive components in the venom of P. nigriventer and other spiders and suggest that our discovery pipeline can be used to identify ion channel-targeting venom peptides with potential as pharmacological tools and to drug leads.

Introduction

Venomous animals are a highly adapted group of organisms whose evolutionary success excelled with the emergence of venom. Spider venoms, in particular, are rich in peptide knottins specialized in modulating, often with high potency and selectivity, voltage-gated ion channels that regulate the physiology of neuronal, muscular and cardiac systems ( Cardoso and Lewis, 2018 ; Cardoso, 2020 ). Although such effects can be deleterious to envenomated animals, venom components can be tailored to selectively modulate ion channels in pathways of complex diseases such as chronic pain, motor neuron disease, and epilepsy. This has been demonstrated for numerous spider venoms ( Smith et al., 2015 ; Cardoso and Lewis, 2018 , 2019 ), including the venom of the infamous South American ctenid spider Phoneutria nigriventer , often referred as Brazilian wandering spider, banana spider or “armed” spider ( Peigneur et al., 2018 ). Besides its clinical relevance due to frequent envenomation cases in Brazil, with approximately 4,000 cases per year ( Isbister and Fan, 2011 ; Gewehr et al., 2013 ), P. nigriventer venom contains peptides that have therapeutic effects in a range of disease models including chronic pain ( Pedron et al., 2021 ; Cavalli et al., 2022 ), Huntington’s disease ( Joviano-Santos et al., 2022 ), glaucoma ( da Silva et al., 2020 ) and erectile dysfunction ( Nunes da Silva et al., 2019 ).

Initial studies of P. nigriventer venom employed fractionation via gel filtration and reversed-phase chromatography to separate the venom into five distinct groups of peptides based on their molecular weight and hydrophobicity properties; these groups were named PhTx1 to PhTx5 ( Peigneur et al., 2018 ). PhTx1–4 comprise cysteine-rich peptides that are active on voltage-gated calcium (Ca V ), sodium (Na V ) and potassium (K V ) channels, while PhTx5 is comprised of short linear peptides, with a total of 34 peptides identified ( Peigneur et al., 2018 ). Proteotranscriptomic studies of P. nigriventer venom revealed additional peptides with high similarity to those previously described, but very few have been characterised pharmacologically ( Cardoso et al., 2003 ; Richardson et al., 2006 ). This represents an obstacle to the exploration of the therapeutic potential of P. nigriventer venom.

Advances in venom-peptide research have yielded high-throughput cellular screens for the discovery and pharmacological characterisation of naturally occurring molecules with activity at ion channels and receptors in physiological pathways ( Cardoso et al., 2015 ; Cardoso et al., 2021 ). These methods require only a small amount of venom compared to more traditional methods and allow the identification of therapeutically relevant peptides in the early stages of the screening. Besides drug development applications, these same bioassays can assist in unravelling the bioactivity of crude and fractionated venoms from biomedically relevant venomous animals to support studies of evolution and antivenom development, but much work remains to be done in this field.

This study aimed to provide a proof-of-concept in applying high-throughput cellular screens for multiple neuronal ion channels along with proteomic studies of fractionated venom to rapidly characterise spider venoms in terms of bioactive components. It was anticipated that such a pipeline would support envenomation and evolutionary studies and the development of therapeutics from animal venoms. The venom of P. nigriventer was selected as a model system due to its medical relevance, the considerable number of therapeutically relevant peptides already uncovered in the venom, and the wide knowledge base available. Our approach enabled identification of potent modulators of voltage-gated ion channels which were classified into four families of neuroactive peptides based on their activity and structures. In addition to the previously characterised neuroactive peptides in the P. nigriventer venom, we identified 27 additional cysteine-rich venom peptides in which neuroactivities are underexplored. This work contributes to the on-going discovery and structure-function characterisation of spider-venom peptides. Moreover, our bioassay pipeline can be used to guide future research into the discovery of venom peptides that modulate the activity of ion channels, and their development as pharmacological tools and drug leads.

Materials and methods

We applied a holistic approach combining methods in high throughput screens for ion channels, venom proteome, venom gland transcriptome and modelling of peptides as described in Figure 1 .

Flowchart of the venom peptide discovery pipeline applied in this study. Expanding from the traditional assay-guided fractionation, we applied HTS bioassays to characterize the pharmacology of venom peptides on multiple ion channels, followed by the identification of peptide masses and primary sequences using proteome and transcriptome. Ultimately, the three-dimensional structure of venom peptides was determined using in silico molecular modelling.

Cell culture

The human neuroblastoma cell line SH-SY5Y was maintained at 37 ° C in a humidified 5% CO 2 incubator in Roswell Park Memorial Institute (RPMI) medium supplemented with 15% foetal bovine serum (FBS) and 2 mM L-glutamine. Replicating cells were sub-cultured every 3–4 days in a 1:5 ratio using 0.25% trypsin/EDTA.

Venom fractionation

Crude venom milked from male and female specimens of P. nigriventer was kindly provided by Prof. Marcus Vinicius Gomez from the Institute of Teaching and Research of Santa Casa de Belo Horizonte, Belo Horizonte, Brazil. Venom (lyophilised, 1 mg) was dissolved in 100 μL Milli-Q water containing 0.05% trifluoroacetic acid (TFA) (Auspep, VIC, AU) and 5% acetonitrile (ACN) and centrifuged at 5,000 × g for 10 min to remove particulates. Venom was fractionated by reversed-phase high performance liquid chromatography (RP-HPLC) using a C18 column (Vydac 4.6 mm × 250 mm, 5 μm, Grace Discovery Sciences, United States) with a gradient of solvent B (90% ACN in 0.045% TFA) in solvent A (0.05% TFA). The gradient was 5% B for 5 min, followed by 20%–40% solvent B over 60 min at a flow rate 0.7 mL min −1 . Peaks were collected every minute, with fraction 1 eluted between 1 and 2 min and so on for the other fractions. Venom fractions were lyophilised before storage at –20°C.

Calcium influx assays

Venom fractions were screened for neuroactivity at human (h) Na V , Ca V 1, Ca V 2 and the α7 subtype of the human nicotinic acetylcholine receptor (nAChR-α7) as previously described ( Cardoso et al., 2015 ). Briefly, SH-SY5Y cells were plated at 40,000 cells per well in 384-well flat clear-bottom black plates (Corning, NY, United States) and cultured at 37 ° C in a humidified 5% CO 2 incubator for 48 h. Cells were loaded with 20 μL per well Calcium 4 dye (Molecular Devices) reconstituted in assay buffer containing (in mM) 140 NaCl, 11.5 glucose, 5.9 KCl, 1.4 MgCl 2 , 1.2 NaH 2 PO 4 , 5 NaHCO 3 , 1.8 CaCl 2 and 10 HEPES pH 7.4 and incubated for 30 min at 37 ° C in a humidified 5% CO 2 incubator. For the hCa V 1 assay, the dye was supplemented with 1 μM ω-conotoxin-CVIF (CVIF) to inhibit Ca V 2, and in the hCav2 assay the dye was supplemented with 10 μM nifedipine to inhibit Ca V 1. For the nAChR-α7 assay, the dye was supplemented with PNU-120596 (Sigma-Aldrich), a positive allosteric modulator of nAChR-α7. Venom fractions were assayed in singleton for each ion channel tested. Fluorescence responses were recorded using excitation at 470–495 nm and emission at 515–575 nm for 10 s to set the baseline, then 300 s after addition of 10% venom fraction serial diluted at 1, 1:10, and 1:100, and for a further 300 s after addition of 50 μM veratridine for hNa V , 90 mM KCl and 5 mM CaCl 2 for hCa V, and 30 μM choline for nAChR-α7.

Venom fractions eluting between 10 and 45 min on RP-HPLC were analysed by mass spectrometry to investigate the masses and primary structures of their peptide components. Native mass determinations were carried out with 20% of each fraction dried by vacuum centrifuge and resuspended in 20 μL 1% formic acid (FA), followed by analysis using by liquid chromatography/tandem mass spectrometry (LC-MS/MS). For identification of primary structures, 20% of each peptide fraction was reduced and alkylated by adding 40 μL of reagent composed of 4.875 mL ACN, 4.5 mL ultrapure water, 0.5 mL 1M ammonium carbonate pH 11.0, 100 μL 2-iodoethanol and 25 μL triethylphosphine, and incubating for 1 h at 37°C. Samples were speed dried in a vacuum centrifuge, and digested with 40 ng/μL trypsin in 50 mM ammonium bicarbonate pH 8.0 and 10% ACN overnight at room temperature. Trypsin was inactivated by adding 50 μL solution containing 50% acetonitrile and 5% formic acid (FA), dried in speed vacuum centrifuge, and resuspended in 1% formic acid.

LC-MS/MS samples were loaded onto a 150 mm × 0.1 mm Zorbax 300SB-C18 column (Agilent, Santa Clara, CA, United States) on a Shimadzu Nano LC system with the outflow coupled to a SCIEX 5600 Triple TOF (Framingham, MA, United States) mass spectrometer equipped with a Turbo V ion source. Peptides were eluted using a 30 min gradient of 1%–40% solvent B (90% ACN/0.1% FA) in solvent A (0.1% FA) at a flow rate of 0.2 mL/min. For MS1 scans, m/z was set between 350 and 2,200. Precursor ions with m/z 350–1,500, charge of +2 to +5, and signals with >100 counts/s (excluding isotopes within 2 Da) were selected for fragmentation, and MS2 scans were collected over a range of 80–1,500 m /z . Scans were obtained with an accumulation time of 250 ms and a cycle of 4 s.

A database of possible peptide sequences produced in P. nigriventer venom glands was compiled using a published venom-gland transcriptome ( Diniz et al., 2018 ), from which open reading frames (ORFs) longer than 30 amino acids were identified and translated by TransDecoder. A list of 200 common MS contaminants was added to the translated ORFs, which was used as a sequence database to compare to mass spectral data using the Paragon algorithm in Protein Pilot 2.2 software (AB SCIEX). We report only peptides for which more than two tryptic fragments were detected with >95% confidence, or where one tryptic fragment was detected, and a secretion signal peptide was predicted by SignalP5.0.

Molecular modelling

Venom peptides identified in this study were selected based on their cysteine-rich scaffold and bioactivity, and their three-dimensional (3D) structure were predicted using the AlphaFold 2 algorithm ( Jumper et al., 2021 ). All 3D structures displayed were from unrelaxed models ranked 1 for each peptide prediction. 3D structures were visualised and analysed using PyMol ( Pymol, 2023 ).

Data analysis

Fluorescence traces from singletons were evaluated using the Maximum-Minimum or Area Under the Curve values generated after addition of ion channel activator. Data were normalised against the negative control (PSS buffer control) and positive control (ion channel activator) for each assay and corrected using the response over baseline from 1 to 5 s. No statistical analyses were required in this study.

Screening of P. nigriventer venom fractions

Fractionation of 1 mg of P. nigriventer ( Figure 2A ) crude venom using RP-HPLC produced numerous peaks eluting between 20% and 40% solvent B, and fractions eluting between 11 and 45 min were selected for pharmacological analysis ( Figure 2B ). Screening using the SH-SY5Y neuroblastoma cell line revealed strong modulation of voltage-gated ion channels including both inhibition or enhancement of ion channel activity ( Figure 2C ). Venom fractions eluting between 18 and 34 min showed strong inhibition of Ca V and Na V activity, while fractions eluting between 41 and 45 min strongly activated Ca V 2 channels ( Figure 2C , top panel). At a dilution of 1:10, these inhibitory effects persisted for both Na V and Ca V 2 channels for fractions eluting at 19–20 min and 26–34 min and was absent for Ca V 1 channels ( Figure 2C , middle panel). Fractions eluting from 21 to 25 min showed a clear preference for inhibiting only Ca V 2 channels ( Figure 2C ). Interestingly, at 1:10 dilution, channel activity enhancement was stronger on Na V channels compared to Ca V 2 channels, suggesting potential concentration-dependent synergistic effects of venom peptides modulating both Na V and Ca V 2 channels. At the highest venom dilution of 1:100, persistent inhibition of Na V channel was observed for fraction 20 (F20), while the remaining inhibitory fractions preferentially inhibited only Ca V 2 channels ( Figure 2C , bottom panel). Channel enhancement persisted for Na V channels in fractions eluting from 41 to 45 min. No potent activity was observed against nAChR-α7 at any venom concentration tested. Overall, inhibitory activity was primarily observed for fractions eluting at shorter retention times (i.e., more hydrophilic compounds), while strong ion channel activation was induced by more hydrophobic peptides with longer RP-HPLC retention times.

Fractionation and activity of P. nigriventer venom. (A) P. nigriventer specimen displaying threat posture (photo copyright Alan Henderson, www.minibeastwildlife.com.au ). (B) RP-HPLC fractionation of 1 mg P. nigriventer venom. (C) Ion channel responses calculated from the area under the curve (AUC) after addition of selective activators for fractions 10 to 45, normalized to responses in the absence of venom fractions. (D, E) Representative fluorescence traces of the intracellular calcium responses of SH-SY5Y cells evoked by KCl + CaCl 2 in the presence of venom fractions 26 and 34 for Ca V 1, fractions 19, 26 and 34 for Ca V 2, and fractions 41–45 for both Ca V 1 and Ca V 2 channels. (F) Representative fluorescence traces of the intracellular calcium responses of SH-SY5Y cells evoked by veratridine and in the presence of venom fractions 19, 26 and 34 and fractions 41–45. (G) Representative fluorescence traces of the intracellular calcium responses of SH-SY5Y cells evoked by choline and in the presence of venom fractions 16 and 40 and fractions 41–45. Grey dotted line indicates the KCl + CaCl 2 , veratridine or choline addition.

Fluorescent traces measured upon addition of venom fractions revealed an increase in intracellular calcium ([Ca 2+ ] i ), suggesting that these venom peptides can activate closed channels as well as enhance the responses of these channels opened using pharmacological intervention ( Figures 2D–G ). This was observed for Ca V responses in the presence of 1 μM CVIF (Ca V 2 inhibitor, Figure 2D ) and 10 μM nifedipine (Ca V 1 inhibitor, Figure 2E ). In the absence of Ca V inhibitors, these [Ca 2+ ] i responses resemble the levels of Ca V 1 responses in Figure 2D as observed for F40–F45 applied in the Na V channels assay ( Figure 2F ). The activities of inhibitory fractions were mostly free from initial [Ca 2+ ] i responses upon venom addition, except for weak inhibitors observed in F19 for Na V and F40 for nAChR-α7 ( Figures 2F, G ).

Identification of peptides in P. nigriventer venom fractions

The venom of P. nigriventer has been extensively characterised in terms of composition and bioactivity ( Diniz et al., 2018 ; Peigneur et al., 2018 ), including neuronal ion channel activity and proteomics, but not by using a combined approach. In this study, by combining these approaches, we were able to rapidly identify 58 peptides and proteins in the venom. Due to the complexity of previous nomenclature for P. nigriventer venom peptides, we refer to them here using both the rational nomenclature developed for spider toxins ( King et al., 2008 ) and an identifying number (e.g., PN367) that is linked to a sequence and a list of previously used names in Supplementary Table S1 . Of the 58 identified amino acid sequences, only eight (15%) are peptides that have had their bioactivity reported in previous studies ( Figure 3A , Supplementary Table S1 ) ( Peigneur et al., 2018 ). These included the known neuroactive components μ-CNTX-Pn1a (Tx1) ( Diniz et al., 2006 ; Martin-Moutot et al., 2006 ), κ-CNTX-Pn1a (Tx3-1, PhK V ) ( Kushmerick et al., 1999 ; Almeida et al., 2011 ), ω-CNTX-Pn1a (Tx3-2) ( Cordeiro Mdo et al., 1993 ), Γ-CNTX-Pn1a [Tx4(5-5)] ( Paiva et al., 2016 ), δ-CNTX-Pn1a [Tx4(6-1)] ( de Lima et al., 2002 ; Emerich et al., 2016 ), δ-CNTX-Pn2c (Tx2-5a) ( Yonamine et al., 2004 ), ω-CNTX-Pn4a (Tx3-6) ( Cardoso et al., 2003 ; Vieira et al., 2005 ) and ω-CNTX Pn3a (Tx3-4) ( Dos Santos et al., 2002 ) ( Figure 3B ). Even among these eight peptides, only a few venom peptides have had their molecular pharmacology characterized in detail ( Peigneur et al., 2018 ), or their activities confirmed using recombinant peptides ( Diniz et al., 2006 ; Paiva et al., 2016 ; Garcia Mendes et al., 2021 ).

Estimated levels of peptide/protein venom components identified in fractions F17 to F45, and their respective bioactivity at Na V and Ca V channels and the nAChR-α7. (A) Proportion of known and unknown venom peptides and other venom components detected in this study. (B) Venom peptides with previously reported bioactivity detected in fractions by mass spectrometry and compared to fraction bioactivity at Na V and Ca V channels and the nAChR-α7. (C) Venom peptides detected in fractions classified according to their cysteine framework I to IX ( Diniz et al., 2018 ), and compared to fraction bioactivity at Na V and Ca V channels and the nAChR-α7.

Most of the identified sequences in this study (74%) represent peptides with unexplored bioactivity; 38 (65%) of the 43 peptides identified have cysteine-rich scaffolds typical of spider-venom peptides ( Figure 3C ). Some of these venom peptides, such as PN367 and PN363, have a type I scaffold ( Diniz et al., 2018 ) and are predicted by Alphafold 2 to fold into cystine-knot scaffolds typical of spider-venom peptides ( King and Hardy, 2013 ) ( Figure 4 ). Scaffolds II-VIII either form elaborated cystine-knot folds with extra disulphide bonds, or alternative structures such as for scaffolds III and IV ( Figure 4 ). Novel peptides with high identity with other toxins and not previously described in P. nigriventer venom included: PN367 displaying identity with a Agelena orientalis venom peptide; PN369 displaying identity with a Lycosa singoriensis venom peptide, and PN365 displaying scaffold III and identity with another Lycosa singoriensis venom peptide ( Supplementary Table S1 ). Additional disulphide-rich scaffolds present in P. nigriventer venom include three peptides predicted by the algorithm HMMER to form a thyroglobulin type 1 repeat domain (E < e −17 in each case), one of which has been previously reported as U24-CNTX-Pn1a; peptide PN370 which displays high identity with a peptide found in venom of the scorpion Scorpiops jendeki and is predicted by the algorithm HMMER to form into a trypsin-inhibitor-like cysteine-rich domain (E < 2e −13 ); and the peptide PN376 that is predicted by HMMER to form a fungal protease inhibitor domain (E < e −6 ) ( Supplementary Table S1 ). Additional new scaffolds identified in this study were named following the previous suggested nomenclature ( Diniz et al., 2018 ) as X (CXCC motif, 12 Cys residues: −C−C−C−C−CXCC−C−C−C−C−C−), XI (12 Cys residues: −C−C−C−CXC−CXC−C−CXC−C−C−), XII (11 Cys residues: −C−C−CXC−CXC−C−C−CXC−C) and XIII (10 Cys residues: −C−C−C−C−C−C−CXC−C−C−), and include the peptides PN376, PN372, PN373 and PN375, and PN370, respectively.

Diversity and estimated levels of cysteine-rich scaffolds identified in highly neuroactive RP-HPLC fractions from the venom of P. nigriventer , and their predicted 3D structures. (A) Fractions 18–20 comprised high levels of scaffolds I, II and VIII represented by the 3D structures of PN367, PN105 and PN267, respectively. (B) Fractions 26 and 27 comprised high levels of scaffolds II, and IV, and an undefined scaffold represented by the 3D structures of PN321, PN350 and PN372, respectively. (C) Fraction 34 comprised high levels of scaffolds I, II, and V represented by the 3D structures of PN003, PN292 and PN028, respectively. (D) Fractions 41 and 42 comprised high levels of scaffolds IV and V represented by the 3D structures of PN381, and PN077 and PN031, respectively.

Only 9% of the identified sequences were peptides with two or fewer Cys residues ( Supplementary Table S1 ). F17 contained a peptide (PN361) matching a C-terminally amidated peptide precursor from Araneus ventricosus identified in a genomic study ( Kono et al., 2019 ). This precursor has 70% sequence identify with the prohormone-1 like precursor from the honeybee Apis mellifera (UniProt {"type":"entrez-protein","attrs":{"text":"P85798","term_id":"190360036","term_text":"P85798"}} P85798 ) which is believed to be cleaved to form three short peptides with neuronal activity. Another short peptide, PN366 identified in F18 and F28–F30, matches a neuropeptide in the sea slug Aplysia californica (UniProt {"type":"entrez-protein","attrs":{"text":"P06518","term_id":"113518","term_text":"P06518"}} P06518 ). Larger proteins were also detected in some fractions; for example, F18 and F31 contained a fragment at 58% and 70% total fraction components, respectively, matching a zinc metalloprotease from the nematode Caenorhabditis elegans (UniProt 55112) which contains a peptidase family M12A domain.

Diversity of neuroactive peptides in P. nigriventer venom

The cysteine-rich scaffolds of venom peptides identified in this study were compared to the classification previously proposed for P. nigriventer venom peptides ( Diniz et al., 2018 ) ( Figures 3C , ​ ,4). 4 ). Peptides in fractions displaying inhibitory properties corresponded to scaffolds I, II, IV, V and VIII, as well as unnamed scaffolds, while peptides in fractions with activation properties comprised mostly the scaffold V. All of these scaffolds are inhibitor cystine knot motifs, except for scaffold IV which had the highest level in F26 represented by the peptide PN350.

Neuroactive peptides with greater hydrophilicity (i.e., those with short RP-HPLC retention times) showed pharmacological properties reminiscent of known spider-derived μ-toxins (F17 and F18) and ω-toxins (i.e., inhibition of Ca V 1 and Ca V 2 channels by F19 and F20) ( Figures 2C , ​ ,5A). 5A ). Major components driving those bioactivities were the pharmacologically characterised peptides μ-CNTX-Pn1a, ω-CNTX-Pn1a and ω-CNTX-Pn3a, as well as additional peptides with unknown activity ( Figure 4A ). As the hydrophilicity of the peptides decrease (i.e., peptides with long RP-HPLC retention times), persistent Ca V 2 inhibition was observed with maximum inhibitory activity in F26 and F27, and with the additional peptide ω-CNTX-Pn4a detected in F24 ( Figures 2C , ​ ,3B, 3B , ​ ,5B). 5B ). Interestingly, venom peptides characterized as K V modulators, such as κ-CNTX-Pn1a, were detected in fractions displaying strong inhibition of calcium influx with potential μ- and ω-pharmacology (fractions 26 and 27); it was not clear if the observed bioactivity was associated to the modulation of K V channels, or to other unexplored peptides in these fractions.

Venom peptide content of highly neuroactive RP-HPLC fractions from the venom of P. nigriventer . (A) Identification of the cysteine-rich peptides and proteins in fractions 17–20 displaying potent inhibition of neuronal Na V and Ca V 2 channels. Positively and negatively charged residues are coloured blue and orange, respectively, hydrophobic residues are green, and cysteines are highlighted in grey box. (B) Identification of the peptide and protein content of the fractions 16 and 27 displaying potent inhibition of neuronal Na V , Ca V 1 and Ca V 2 channels. (C) Identification of the peptide and protein content of the fraction 34 displaying potent inhibition of neuronal Na V , Ca V 1 and Ca V 2 channels. (D) Identification of the peptide and protein content of the fraction 34 displaying potent activation of neuronal Na V and Ca V 2 channels. Sequences labelled with a red asterisk (*) at the C-terminal are likely C-terminally amidated.

Neuroactive peptides presenting more hydrophobic structures showed properties of μ and ω-peptides, but with preference for Ca V 2 channels as observed for fraction 34 in which the peptide Γ-Pn1a is the major component, consistent with its previously observed modulation of multiple cation channels ( Paiva et al., 2016 ); and of δ-peptides as observed in fractions 41 to 45, in which major components included the peptides δ-Pn1a and δ-Pn2c ( Figures 2C–F , and Figures 5C, D ). Notably, the main components of some of the most neuroactive fractions are peptides with unexplored bioactivity, e.g., fraction 26 ( Figures 2C , ​ ,4, 4 , ​ ,5 5 ).

Pharmacological groups

Our approach allowed classification of P. nigriventer venom peptides into four major groups based on their bioactivity ( Figure 6 ; Table 1 ). Group 1 is comprised of μ and ω peptides with scaffold type VIII and more hydrophilic properties as they eluted between F17 and F21. As representatives from this group, μ-CNTX-Pn1a and ω-CNTX-Pn3a have a potential “KR electrostatic trap”, a pharmacophore described in spider-venom peptides that modulate ion channels ( Hu et al., 2021 ; Wisedchaisri et al., 2021 ), in their primary and tertiary structures ( Figure 6A ). This pharmacophore is likely composed of residues R61, K67, K70, K71, R74 and R75 in μ-CNTX-Pn1a and residues K54, K56, R59, K65, K70, R71, K73 and K74 in ω-CNTX-Pn3a. Within this group, the ω-CNTX-Pn3a homologue PN319 differs at three positions, making it an interesting candidate for further characterisation.

Pharmacological groups identified in the most active venom fractions highlighting the “KR electrostatic trap” pharmacophore common to spider toxins that modulate the activity of ion channels. (A) Group 1 is represented by μ- and ω-spider-venom peptides with large and complex type VIII scaffold. (B) Group 2 is represented by κ- and ω-spider-venom peptides with type II and VII scaffolds. (C) Group 3 is represented by γ-spider-venom peptides with type V scaffold. (D) Group 4 is represented by δ-spider-venom peptides displaying a type V scaffold. K and R residues located in the C-terminal region of these peptides and grouped on a positively charged face are highlighted in red in the sequences and in red tubes in the corresponding 3D structures. Arrows shows the cysteine-bridge connection forming the cyclic peptide structures predicted for PN028 and PN031.

Pharmacological groups identified in this study with respective pharmacological types, cysteine-rich scaffold types, and representative venom peptides described in the literature. Unexplored peptides within each group are described in Figure 5 and/or Supplementary Table S1 .

Group 2 comprises κ and ω peptides that eluted between F17 and F28, with scaffold types II and VII ( Figure 6B ). As representatives from this group, peptides κ-CNTX-Pn1a, ω-CNTX-Pn1a and ω-CNTX-Pn4a also contain a “KR trap” pharmacophore comprised of residues R20, K23, K34, K35 and K36 for ω-Pn1a; R21, K24, K35 and K36 for κ-Pn1a; and K42, R47, K48, K49, K51, K53 and K54 for ω-Pn4a. In this group, PN107 differs from κ-CNTX-Pn1a by only two residues and is an interesting peptide for further exploration.

Group 3 is comprised of more hydrophobic Γ peptides that eluted in F33–F36 and possess a type V scaffold ( Figures 3C–D , ​ ,6C). 6C ). It is represented by Γ-CNTX-Pn1a with a potential “KR trap” comprising residues K35, R41, K42 and K43. Although Γ peptides modulate N-methyl-D-aspartate (NMDA) glutamate receptors, Γ-CNTX-Pn1a has also been reported as a β-peptide that inhibits Na V channels ( Paiva et al., 2016 ), which agrees with the results from our high-throughput ion channels assays ( Figures 2C–F , ​ ,3). 3 ). Interestingly, Γ-CNTX-Pn1a predicted 3D structure formed a cyclic structure in which the N-terminal cysteine formed a disulfide bridge with C-terminal cysteine ( Figures 4C , ​ ,6C). 6C ). These same fractions contain other ICK peptides including PN003 and PN292 with scaffold types I and II, respectively; their pharmacological targets have not been explored but they likely contribute to the strong inhibition of Ca V channels by F34 ( Figures 2 , ​ ,3, 3 , ​ ,4 4 ).

Group 4 is composed of very hydrophobic δ peptides that elute in F40–F45 and possess a type V scaffold ( Figure 2B , ​ ,6D). 6D ). It is represented by δ-CNTX-Pn1a with potential “KR trap” comprising residues K43, K44, and K45 ( Figure 6D ). In this group we also identified δ-CNTX-Pn2c which differs not only in primary structure but also in the scaffold V tertiary structure by presenting a non-cyclic structure compared to the cyclic structure predicted for δ-CNTX-Pn1a connected by the N- and C-terminal cysteines ( Figures 4D , ​ ,6D). 6D ). Beyond these known peptides, this group comprised interesting unexplored peptides such as PN032 and PN023 showing δ peptide domains and differing from Γ-CNTX-Pn1a by 12 and 11 residues, respectively.

Spiders are one of the most speciose venomous taxa, with >50,000 characterised species (see World Spider Catalog, https://wsc.nmbe.ch/statistics/ ). Their venoms are rich in neuroactive peptides that target a wide range of neuronal ion channels and receptors using mechanisms distinct from those of neurotoxins from other venomous animals such as cone snails and scorpions. The exploration of venom peptides targeting ion channels and receptors provides novel opportunities for the development of pharmacological tools to understand disease mechanisms ( Cardoso and Lewis, 2018 ; Cardoso, 2020 ) as well as provision of leads for development of therapeutics ( King, 2011 ) and bioinsecticides ( Smith et al., 2013 ).

Spiders are classified in two major groups, or infraorders ( King, 2004 ): Mygalomorphae, or so-called “primitive spiders”, includes the family Theraphosidae, or tarantulas, which are the most well studied spider venoms due to the large-size and long lifespan (often >20 years) of these spiders. Araneomorphae, or “modern spiders,” comprise >90% of all extant spider species, including the family Ctenidae in which P. nigriventer resides. Notably, despite their much greater species diversity, araneomorph venoms are underexplored compared to mygalomorphs due to their smaller size and shorter lifespan (typically 1–2 years). Our data, and those of others ( Binford et al., 2009 ; Zhang et al., 2010 ; Diniz et al., 2018 ; Peigneur et al., 2018 ), showed a great diversity of both pharmacological actions and cysteine scaffolds in araneomorph venom, which may have facilitated the highly successful araneomorph radiation. Our data also suggests Araneomorphae’s venoms may be a rich source of unique venom peptides with more diverse structures and pharmacological functions and additional biotechnological and therapeutic applications to Mygalomorphae’s venoms.

The venom from P. nigriventer comprises many exceptional peptides drug leads under development for treating a range of complex neuro disorders ( Peigneur et al., 2018 ). These peptides have been evaluated in pre-clinical models and demonstrated interesting therapeutic efficacy in reverting or preventing conditions for which treatments are limited or unavailable. For example, ω-Pn2a and ω-Pn4a showed efficacy in treating painful neuropathies such as fibromyalgia and chronic post-ischemia pain, respectively ( Pedron et al., 2021 ; Cavalli et al., 2022 ), ω-Pn4a also improved motor movement and neuroprotection in Huntington’s disease ( Joviano-Santos et al., 2022 ). The engineered peptide PnPP-19 derived from the venom peptide δ-Pn2a was efficacious in treating glaucoma ( da Silva et al., 2020 ) and erectile dysfunction ( Nunes da Silva et al., 2019 ). In our study, these therapeutic peptides showed bioactivity at neuronal Na V and Ca V channels, which greatly supports our investigative platform for the discovery of venom peptides useful for the development of efficacious drugs.

Investigative pipelines in venomic studies often focus on the elucidation of venom components based on their structures but lack clear strategies to investigate venom bioactivities ( von Reumont et al., 2022 ). Investigations using fractionated venom ( Cardoso et al., 2015 ; Cardoso et al., 2017 ; Estrada-Gomez et al., 2019 ; Cardoso et al., 2021 ) provides more defined biological functions than using crude venom due to the immense pharmacological diversity of venom, which often contains venom components with opposing activity as well as components that act synergistically ( Raposo et al., 2016 ). Considering the large number of extant spiders and consequently the exceptionally large number of venom components available for investigation, high-throughput (HT) functional bioassays are essential for developing a holistic understanding of venom pharmacology, and they provide a complement to venomic studies.

A recent study by us using HT bioassays to investigate the ion channel targets of Australian funnel-web spider venoms recaptured current taxonomy and revealed potential drug targets to treat severely envenomated patients ( Cardoso et al., 2022 ). In this present study, we also demonstrated the feasibility of applying HT functional bioassays to investigate spider venom components that mediated the activity of voltage-gated ion channels. We were able to capture all known venom components and associated bioactivities using a HT functional assay as well as several new unexplored venom peptides that warrant further exploration. This was achievable only by combining HT bioassays with transcriptomic and proteomic approaches. Although this pipeline provides a robust holistic overview of spider venoms, bioactive components are present in varying concentrations in each fraction, which may affect bioactivity through synergistic effects, and overlook the activity of less abundant components.

The complexity of the cysteine-rich scaffolds in P. nigriventer venom peptides unraveled in this study suggests that further exploration utilising recombinant or synthetic peptides might be challenging but essential, and these could also benefit from modern strategies utilizing HT recombinant expression or chemical synthesis ( Pipkorn et al., 2002 ; Turchetto et al., 2017 ). In tandem with automated whole-cell patch-clamp electrophysiological studies, this will build a pipeline to further investigate known and new peptides in the venom of P. nigriventer and allow selection of candidates with biotechnological potential. The putative “KR trap” pharmacophores identified in those venom peptides warrants further exploration of the structure-function relationships of the diverse pharmacological groups found in the venom of P. nigriventer.

In conclusion, we demonstrated that the introduction of HT functional bioassays in venomic studies is essential to provide a more complete understanding of venom components in terms of structure and function. It also allows venom peptides to be ranked for further investigation based on their bioactivity and structural diversity, which is not possible via transcriptomic and proteomic studies alone. Furthermore, this study provides a guide to assist the exploration of neuroactive venoms from other animals, in particularly for the underexplored araneomorph spiders.

Acknowledgments

We thank Mr. Alun Jones and Dr. Kuok Yap (Institute for Molecular Bioscience, The University of Queensland) for assistance with mass spectrometry experiments.

Funding Statement

This work was supported by The University of Queensland, the Australian National Health and Medical Research Council (Ideas Grant GNT1188959 to FC; Principal Research Fellowship APP1136889 to GK), and the Australian Research Council (Discovery Grant DP200102867 to AW; Centre of Excellence Grant CE200100012 to GK).

Data availability statement

Author contributions.

Conceptualization: FC; design, conduct, and analysis of experiments: FC and AW; MG contributed with the P. nigriventer crude venom. drafting of manuscript: FC. All authors contributed to reviewing and editing of the manuscript and approved the final version for submission.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmolb.2023.1069764/full#supplementary-material

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Deadly Venom From Spiders and Snakes May Also Cure What Ails You

Efforts to tease apart the vast swarm of proteins in venom — a field called venomics — have burgeoned in recent years, leading to important drug discoveries.

A rattlesnake at the Arizona-Sonora Desert Museum, which keeps snakes and scorpions for their venom. Credit... Ash Ponders for The New York Times

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By Jim Robbins

• Published May 3, 2022 Updated May 6, 2022

TUCSON, Ariz. — In a small room in a building at the Arizona-Sonora Desert Museum, the invertebrate keeper, Emma Califf, lifts up a rock in a plastic box. “This is one of our desert hairies,” she said, exposing a three-inch-long scorpion, its tail arced over its back. “The largest scorpion in North America.”

This captive hairy, along with a swarm of inch-long bark scorpions in another box, and two dozen rattlesnakes of varying species and sub- species across the hall, are kept here for the coin of the realm: their venom.

Efforts to tease apart the vast swarm of proteins in venom — a field called venomics — have burgeoned in recent years, and the growing catalog of compounds has led to a number of drug discoveries. As the components of these natural toxins continue to be assayed by evolving technologies, the number of promising molecules is also growing.

“A century ago we thought venom had three or four components, and now we know just one type of venom can have thousands,” said Leslie V. Boyer, a professor emeritus of pathology at the University of Arizona. “Things are accelerating because a small number of very good laboratories have been pumping out information that everyone else can now use to make discoveries.”

She added, “There’s a pharmacopoeia out there waiting to be explored.”

It is a striking case of modern-day scientific alchemy: The most highly evolved of natural poisons on the planet are creating a number of effective medicines with the potential for many more.

One of the most promising venom-derived drugs to date comes from the deadly Fraser Island funnel web spider of Australia, which halts cell death after a heart attack .

Blood flow to the heart is reduced after a heart attack, which makes the cell environment more acidic and leads to cell death. The drug, a protein called Hi1A, is scheduled for clinical trials next year. In the lab, it was tested on the cells of beating human hearts. It was found to block their ability to sense acid, “so the death message is blocked, cell death is reduced, and we see improved heart cell survival,” said Nathan Palpant, a researcher at the University of Queensland in Australia who helped make the discovery.

If proven in trials, it could be administered by emergency medical workers, and might prevent the damage that occurs after heart attacks and possibly improve outcomes in heart transplants by keeping the donor heart healthier longer.

“It looks like it’s going to be a heart attack wonder drug,” said Bryan Fry, an associate professor of toxicology at the University of Queensland, who is familiar with the research but was not involved in it. “And it’s from one of the most vilified creatures” in Australia.

The techniques used to process venom compounds have become so powerful that they are creating new opportunities. “We can do assays nowadays using only a couple of micrograms of venom that 10 or 15 years ago would have required hundreds of micrograms,” or more, Dr. Fry said. “What this has done is open up all the other venomous lineages out there that produce tiny amounts of material.”

There is an enormous natural library to sort through. Hundreds of thousands of species of reptile, insect, spider, snail and jellyfish, among other creatures, have mastered the art of chemical warfare with venom. Moreover, the makeup of venom varies from animal to animal. There is a kind of toxic terroir: Venom differs in quantity, potency and proportion and types of toxin, according to habitat and diet, and even by changing temperatures due to climate change.

Venom is made of a complex mix of toxins, which are composed of proteins with unique characteristics. They are so deadly because evolution has honed their effectiveness for so long — some 54 million years for snakes and 600 million for jellyfish.

Venom is the product of a biological arms race over that time; as venom becomes more deadly, victims evolve more resistance, which in turn makes venom even deadlier. Humans are included in that dynamic. “We are made of protein and our protein has little complex configurations on it that make us human,” said Dr. Boyer, who founded the Venom Immunochemistry, Pharmacology, and Emergency Response Institute, or VIPER. “And those little configurations are targets of the venom.”

The specific cellular proteins that the venom molecules have evolved to target with pinpoint accuracy are what make the drugs derived from them — which use the same pathways — so effective. Some proteins, however, have inherent problems that can make new drugs from them unworkable.

There is usually no need to gather venom to make these drugs. Once they are identified, they can be synthesized.

There are three main effects from venom. Neurotoxins attack the nervous system, paralyzing the victim. Hemotoxins target the blood and local tissue toxins attack the area around the site of poison exposure.

Numerous venom-derived drugs are on the market. Captopril, the first, was created in the 1970s from the venom of a Brazilian jararaca pit viper to treat high blood pressure. It has been successful commercially. Another drug, exenatide, is derived from Gila monster venom and is prescribed for Type 2 diabetes. Draculin is an anticoagulant from vampire bat venom and is used to treat stroke and heart attack.

The venom of the Israeli deathstalker scorpion is the source of a compound in clinical trials that finds and illuminates breast and colon tumors.

Some proteins have been flagged as potential candidates for new drugs, but they have to journey through the long process of manufacture and clinical trials, which can take many years and cost millions of dollars. In March, researchers at the University of Utah announced that they had discovered a fast-acting molecule in cone snails . Cone snails fire their venom into fish, which causes the victims’ glucose levels to drop so rapidly it kills them. It holds promise as a drug for diabetes. Bee venom appears to work with a wide range of pathologies and has recently been found to kill aggressive breast cancer cells .

In Brazil researchers have been looking at the venom of the Brazilian wandering spider as a possible source of a new drug for erectile dysfunction — because of what happens to human victims when they are bit. “A characteristic of their envenomation is that males get extraordinary painful, incredibly long-lasting erections,” Dr. Fry said. “They have to separate it from its lethal factor, of course, and find a way to dial it back.”

Some scientists have long suspected that important secrets are locked up in venom. Scientific interest first surfaced in the 17th century. In the mid-18th century the Italian physician and polymath Felice Fontana added to the body of knowledge with his treatise, and in 1860 the first research to look at venom components was conducted by S. Weir Mitchell in Philadelphia.

The medicinal use of venom has a long history, often without scientific support. Venom-dipped needles are a traditional form of acupuncture. Bee sting therapy, in which a swarm of bees is placed on the skin, is used by some natural healers. The rock musician Steve Ludwin claims to have routinely injected himself with diluted venom, believing it to be a tonic that builds his immune system and boosts his energy.

The demand for venom is increasing. Ms. Califf of the Arizona-Sonora Desert Museum said she had to travel to the desert to find more bark scorpions, which she hunts at night with a black light because they glow in the dark. Arizona, Dr. Boyer said, is “venom central,” with more venomous creatures than in any other U.S. state, making it well suited for this kind of production.

Scorpion venom is harvested by applying a tiny electrical current to the arachnid, which causes it to excrete a small drop of the amber liquid at the tip of its tail. With snakes, venom glands are gently massaged as they bare their fangs over a martini glass. After they surrender their venom, the substance is sent to researchers around the globe.

Pit vipers, including rattlesnakes, have other unusual adaptations. The “pit” is the site of the biological equipment that allows snakes to sense the heat of their prey. “You can blindfold a snake and it will still strike the target,” Dr. Boyer said.

But it’s not just venom that’s far better understood these days. In the last few years, there has been a well-heeled and concerted search for antivenom.

In 2019 the Wellcome Trust created a $100 million fund toward the pursuit. Since then there have been numerous research efforts around the world looking for a single universal treatment — one that can be carried into remote areas to immediately help someone bitten by any type of venomous snake. Currently, different types of snakebites have different antivenom.

It has been difficult. The wide array of ingredients in venom that benefit new drug research has also made it difficult to find a drug that can neutralize them. One promising universal antivenom, varespladib, is in clinical trials.

Experts hope the role of venom will lead to more respect for the fear-inducing creatures who create them. Dr. Fry, for his work on anticoagulants, is studying the venom of Komodo dragons, which, at 10 feet long and more than 300 pounds, is the largest lizard in the world. It is also highly endangered.

Work on the Komodo, “allows us to talk about the broader conservation message,” he said.

“You want nature around because it’s a biobank,” he added. “We can only find these interesting compounds from these magnificent creatures if they are not extinct.”

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Brazilian Wandering Spider Size: Explained & Compared With Other Spiders

Last Updated on April 10, 2023 by Amin Tawar

Brazilian Wandering Spider Length

Phoneutria is a genus of combative and poisonous spiders, sometimes known as Phoneutria, armed spiders (“armadeiras” in Portuguese). 

There are eight recognized species, with Phoneutria fera and Phoneutria nigriventer being the most hazardous. They are hairy and typically dark brown, with some having brilliant red hairs on their venomous glands. 

Additionally, these species of spiders have subtle differences in appearance but can be distinguished by their size. 

They generally support a leg span of up to 15 cm (6 in) and a body length of up to 5 cm (2 in). They maintain an aggressive defensive stance, lifting their front legs straight into the air.

Brazilian Wandering Spider Weight

The Brazilian Wandering Spider can grow to have a leg span of up to 4 to 6 inches, as we have already mentioned. 

They are large, hairy spiders with a spindly appearance, and they have eight eyes, including two large eyes.

Additionally, these spiders move quickly and only weigh a little under an ounce. However,  they do have strong, spiny legs, and when they are angry, they show off their distinctive red jaws. 

Brazilian Wandering Spider Max Size

Brazilian Wandering, Armed, and Banana Spiders are all members of the Phoneutria family, as we’ve already mentioned. 

The Brazilian Wandering Spider is a large spider with a body size of up to 2 inches, but it weighs much less than 1 ounce. 

In terms of their maximum length, which can reach 7 inches when their legs are included, they are undoubtedly not small but are still reasonably on the lighter side given their tendency to move quickly and rapidly.

Brazilian Wandering Spider Size Comparison To A Human Hand 

Even though Wandering spider bites rarely result in death, they are notorious for being deadly. A human bitten by one of these spiders might experience initial signs like an intense burning pain, sweating, and goosebumps.

Within 30 minutes, symptoms spread throughout the body, including nausea, high or low blood pressure, a fast or slow heartbeat, and more. 

Therefore, it is crucial for us to understand how they appear in relation to our size, specifically the size of our hands.

So, as we have mentioned before The Brazilian Wandering Spider is a large spider with a body size of up to 2 inches, but it weighs much less than 1 pound. In terms of their maximum length, which can reach 7 inches when their legs are included. On average, an adult male’s hand measures 7.6 inches in length, from the tip of the longest finger to the crease beneath the palm.

Whereas, An adult female’s hand measures 6.8 inches on average. Comparing these specifics we can conclude that the Brazilian wandering spider is smaller in appearance than an average human hand. Irrespective of this they are much more harmful to mankind. 

Brazilian Wandering Spider Vs Sydney Funnel Web size comparison

Among the top five deadliest spiders in the world are the Sydney funnel-web spider and the Brazilian wandering spider. 

Coming to their size, the Sydney funnel-web spiders are sizable, they are black spiders with hairy legs and smooth bodies. A female Sydney funnel web spider can get as long as 2 inches, while their male counterparts are slightly shorter. 

Whereas, as we have mentioned, an adult Brazilian wandering spider grows up to 2 inches long. They also have red hairs on their bodies, which makes them look more striking.

They also have red hairs on their bodies, which makes them look more striking.  In comparison, Brazilian wandering spiders are typically smaller in size than Sydney funnel-web spiders. However, the Brazilian wandering spiders are more aggressive than the Sydney funnel web.

Brazilian Wandering Spider Vs Brown Recluse Size Comparison

The Brazilian Wandering Spider is a large brown spider that resides primarily on banana leaves. 

While brown recluse spiders are typically seen moving about, not in webs, but walking or running. In terms of size, female brown recluse spiders can reach lengths of up to 1/4 inch without their legs; when their legs are included, they measure about 1 inch. 

The Brazilian Wandering Spider, in contrast, has a body size that can reach 2 inches, but it weighs less than 1 pound. When their legs are included, they can grow to a maximum length of 7 inches.

When the specifics are compared, we can see that the Brazilian spider is larger than the brown recluse spider.

Brazilian Wandering Spider Vs Black Widow Size Comparison

Both spiders are extremely venomous. However, when comparing sizes, the Brazilian wandering spiders are larger than the black widow. 

While the average length of a black widow is between 1.5 and 2 inches. Whereas the Brazilian wandering spiders can grow to a body size of 2 inches, they weigh less than 1 pound. 

They can reach a maximum length of 7 inches when their legs are included. These specifics make their sizes significantly different from one another.

Brazilian Wandering Spider Vs Tarantula Size Comparison

The Brazilian wandering spiders’ hairs frequently give the impression that they are even more prominent. Comparing them to the tarantula family, which includes most of the largest spiders in the world.

The tarantula clearly outweighs the other species in terms of size. Brown tarantulas have large, heavy bodies and can have leg spans of over 4 inches. A tarantula’s adult weight can reach 3 oz. The Goliath can reach a maximum size of 11 inches in length, a 12-inch leg span, and 6 ounces of weight.

Brazilian Wandering Spider Vs Six Eyed Sand Spider Size Comparison

The medium-sized six-eyed sand spider has legs up to 4 inches long and a body between 1 and 2 inches wide. Deserts and other sandy areas are where you can find them. 

In contrast, the Brazilian Wandering Spider is a sizable brown spider with highly toxic venoms. The Brazilian wandering spiders, as previously mentioned, can reach a body size of 2 inches and weigh less than 1 ounce. 

When their legs are included, they can grow to a maximum length of 7 inches. These details allow us to draw the conclusion that the Brazilian wandering spider is smaller than the six-eyed sand spider.

And that was everything you need to know about the size of Brazilian Wandering spiders. I hope this article was helpful and you got something valuable from it.

Thank You For Reading!

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Brazilian Wandering Spider vs Tarantula See Who Wins

Welcome ladies and gentlemen to this thrilling matchup between the Brazilian Wandering Spider and the Tarantula! Both renowned for their unique characteristics, these arachnids are ready to showcase their skills in a fierce battle. The crowd is buzzing with excitement, and anticipation fills the air as we prepare for this epic showdown. Let the fight begin!

Matchup Stats

Make your pick, see who wins, scientific stats, contender 1: brazilian wandering spider.

The Brazilian Wandering Spider, also known as the banana spider, is a highly venomous spider found in South and Central America. It is known for its aggressive behavior and wandering tendencies, often found in homes and gardens. The spider can grow up to 5 inches in leg span and has distinctive markings on its body, including a red spot on its abdomen. Its venom can cause paralysis and even death in humans.

Contender 2: Tarantula

Tarantulas comprise a group of large, hairy spiders that are found in various parts of the world, predominantly in the tropics. They possess eight legs, two body parts (cephalothorax and abdomen), and are known for their pronounced fangs, which they use to inject venom into their prey. Despite their menacing appearance, tarantulas are generally not harmful to humans, as their venom is weaker than that of a typical bee.

Fun Fact : Tarantulas are known for their unique defensive tactic where they can flick off tiny, barbed hairs from their abdomen when threatened, which can irritate the skin or eyes of a potential predator.

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Brazilian wandering spider vs tarantula, start live matchup, view more matches.

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Key Differences between Brazilian Wandering Spider and Tarantula

• Venomous traits : While both spiders have venom, the Brazilian Wandering Spider is infamous for its highly toxic venom and aggressive behavior, making it one of the most venomous spiders in the world. Tarantulas, on the other hand, while capable of biting, generally possess less potent venom and are known for their relatively docile and non-aggressive nature.
• Body shape : Brazilian Wandering Spiders have a more elongated and slender body shape compared to Tarantulas, which are known for their robust and chunky bodies.
• Coloration : Brazilian Wandering Spiders showcase a variety of colors, including shades of brown, black, and sometimes even yellow, whereas Tarantulas can exhibit a wider range of colors, including black, brown, gray, red, and even blue.
• Pedipalps : The Brazilian Wandering Spider has prominent pedipalps (sensory appendages near their mouthparts) that appear elongated and more visible than those of the Tarantula, which typically have shorter and more inconspicuous pedipalps.
• Size : The Brazilian Wandering Spider is generally smaller than the Tarantula, with an average body length ranging between 1.5 and 2 inches, while Tarantulas can vary greatly in size, often growing up to 4 to 6 inches or even larger.
• Leg length : Tarantulas tend to have longer and thicker legs in comparison to the Brazilian Wandering Spider, which possesses relatively shorter and thinner legs.