The next generation of antivenoms is almost here

Good news! It looks like antivenoms are soon becoming extremely effective with this latest research.

I just blogged here about a similar new, very successful approach! I believe, these two research articles represent a major breakthrough in antivenom development.

"... for the new study, the team zeroed in on one group in particular: cobras in India, a country that bears the greatest burden of snakebite death in the world and where the current antivenom all too often falls short.

Small doses of a mixture of just five nanobodies saved mice from lethal doses of venom from India’s deadliest cobra species, even when administered to the animals half an hour after the toxins. “Mice that were paralyzed or had typical neurotoxic symptoms would revert to a completely asymptomatic state ,” ..."

"... now developed a recombinant, nanobody-based antivenom that offers broad protection against venom from geographically diverse cobra and king cobra species in India. ...

Unlike conventional antivenoms, these recombinant antibodies can be manufactured using microbial and humanised expression systems without repeatedly immunising animals like horses. Additional antibody components can be added to expand protection to other medically important snakes, allowing future recombinant antivenoms to be tailored for different regions or species. ..."

From the abstract:

"Snakebite envenoming causes more than 100,000 deaths annually, with India bearing nearly half of this burden.

Current equine plasma–derived antivenoms suffer from variable efficacy, safety concerns, and limited cross-neutralization of geographically diverse venoms.

Here, we report a rationally designed recombinant antivenom composed of five nanobodies (VHHs) that target the α-neurotoxins, cytotoxins, and phospholipases A2 prevalent in the venoms of cobra and king cobra species from India.

These VHHs were previously identified and functionally validated against homologous toxin families from African elapids.

In murine preincubation and rescue models of snakebite envenoming, the cocktail prevented mortality after injection with venom from the monocled cobra (Naja kaouthia), both king cobra species (Ophiophagus kaalinga and Ophiophagus hannah) from the Western Ghats and Northeast India, and pan-Indian populations of spectacled cobra (Naja naja).

These findings demonstrate the feasibility of developing broad-spectrum nanobody-based recombinant antivenoms with continent-wide coverage as a safe and regionally adaptable biologic for snakebite envenoming therapy."

ScienceAdviser

Engineered antibodies offer broad protection against deadly cobra toxins (original news release)

Oligoclonal nanobody-based recombinant antivenom protects mice challenged with venom from cobras and king cobras from India (no public access)

Antivenom derived from rattlesnake blood can neutralize other venomous snake species

Good news! This might be a breakthrough! It was already discovered in 2022.

It has been known for a long time that snakes are protected from their own venom. Why was this fact not explored much earlier?

"Antivenom derived from rattlesnake blood can “powerfully neutralize” venom from a range of venomous snake species, finds a new study published in PNAS; researchers found that combinations of toxin-blocking proteins from the snake’s blood were ~10X times more potent than a current commercial antivenom."

"... researchers discovered a new approach to treating venomous snake bites—using the same toxin-blocking proteins that snakes evolved to protect themselves. The team found that specific combinations of blood proteins from western diamondback rattlesnakes provided unprecedented neutralizing power against the venom of multiple dangerous snake species. ...

Snakebites remain one of the world's most neglected tropical diseases. ...

In 2022, ... lab found part of the answer: a single protein called FETUA-3 that blocked the activity of many metalloproteinase toxins in the western diamondback’s venom. FETUA-3 also bound to and inhibited the toxins of venoms from several other rattlesnakes. ...

For the new study, ... investigated the individual roles of all FETUA proteins. They found that while one FETUA protein might reduce bleeding and another might affect enzyme activity, no one FETUA protein completely prevented death from a bite.

However, combining several of these proteins dramatically increased their ability to neutralize venom’s damaging effects. ..."

From the significance and abstract:

"Significance

Snakebite remains an undertreated tropical disease that affects over one million people annually, and new therapeutic approaches are needed. Here, we develop an approach to viper antivenoms inspired by the observations that these snakes are typically resistant to the hemorrhagic and lethal effects of their own venoms and that this resistance can be transferred to experimental animals through snake sera. We show that a small set of serum metalloproteinase inhibitors from the Western Diamondback rattlesnake are potent inhibitors of the lethality of its own venom, and able to block the lethality of other rattlesnakes and evolutionarily distant vipers. Recombinant natural antitoxins offer a promising approach for formulating more potent viper antivenoms.

Abstract

Snakebite maims or kills several hundred thousand people each year.

For more than a century, treatment has relied on antivenoms derived from animals immunized with whole venoms, but their efficacy, safety, and availability are highly variable, and it is often not well understood which specific venom components must be inhibited to prevent mortality and major morbidities.

New therapeutic approaches are needed.

Here, we take an evolutionary approach to antivenom design inspired by the longstanding observation that vipers have evolved serum-borne toxin inhibitors that confer resistance to their own venoms. We have investigated the abilities of a family of four rattlesnake metalloproteinase (MP) inhibitors derived from the ancestral serum glycoprotein Fetuin-A (FETUAs) to neutralize the enzymatic, hemorrhagic, and lethal activities of viper venoms.

We find that while certain individual FETUA proteins are able to inhibit enzymatic or hemorrhagic activity, they are unable or only partially able to inhibit venom lethality.

However, we show that specific combinations of FETUA proteins complement one another’s activities and are sufficient to fully neutralize rattlesnake venom lethality with approximately 10 times greater potency than commercial antivenom.

Moreover, we demonstrate that FETUA proteins are well conserved among viper subfamilies and that rattlesnake FETUAs are able to inhibit the MPs and neutralize the lethality of several evolutionarily distant pit viper or true viper venoms.

Our results highlight the critical importance of inhibiting MPs in hemorrhagic venoms and the potential general utility of combinations of naturally evolved, recombinant MP inhibitors in the treatment of viper snakebite."

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Scientists Discover an Antidote to Lethal Snake Bites that Comes Straight from the Source (original news release) "A new UMD-led study provides a blueprint for the next generation of antivenoms—using snakes’ natural molecular defenses against their own deadly venom."

Nature’s antivenom: Combinations of conserved rattlesnake serum metalloproteinase inhibitors block the lethal action of viper venoms (open access)

Nigeria’s Fatal Antivenom Shortfall. Really!

Maybe it is time to systematically and routinely kill some of these snakes and destroy their nesting places!

How about eradication of dangerous snakes?

"The death of a high-profile Nigerian singer from a snakebite has ignited widespread outrage over the country’s inadequate supply of antivenom and the need for a national snakebite strategy ..."

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Scientists develop a second, universal antivenom that neutralizes the neurotoxins of 19 of the world's deadliest snakes in 2025

Good news! Amazing stuff! I blogged here in February about an earlier, universal antivenom!

So now we have to broadly effective universal antivenoms against snake bites, and both came out in 2025!

The hero is Tim Friede [Friede is German for peace]!

"By using antibodies from a human donor [Time Friede] with a self-induced hyper-immunity to snake venom, scientists have developed the most broadly effective antivenom to date, which is protective against the likes of the black mamba, king cobra, and tiger snakes in mouse trials. Described in the journal Cell, the antivenom combines protective antibodies and a small molecule inhibitor and opens a path toward a universal antiserum. ...

"The donor, for a period of nearly 18 years, had undertaken hundreds of bites and self-immunizations with escalating doses from 16 species of very lethal snakes that would normally kill a horse," ..."

From the highlights and abstract:

"Highlights

• We report a systematic method for the construction of a broad-spectrum snake antivenom

• Broadly neutralizing antitoxin antibodies were identified from a venom-immune subject

• Broad toxin neutralization involved recognition of conserved toxin-receptor interfaces

• A 3-agent cocktail blocked envenomation by 19 diverse WHO Category 1 and Category 2 snakes

Summary

Snake envenomation is a neglected tropical disease, with 600 species causing over 100,000 deaths and 300,000 permanent disabilities in humans annually.

Broadly neutralizing antibodies and broad chemical inhibitors have been proposed as solutions, but how to develop a therapeutically effective cocktail and the number of required components have been unclear.

To address this gap, we iteratively recovered two broadly neutralizing antivenom antibodies from the memory B cells of a hyperimmune human donor with extensive snake venom exposure.

The antibodies recognized conserved neutralizing epitopes on prevalent long and short snake neurotoxins, with crystal structures revealing antibody mimicry of the interfaces between these neurotoxins and their host target, the nicotinic acetylcholine receptor.

We combined and tested these antibodies and the phospholipase inhibitor varespladib. A 3-component cocktail rescued animals from whole-venom challenge of all species in a 19-member WHO Category 1 and Category 2 elapid diversity set, with complete protection against most snakes observed."

Scientists develop antivenom that neutralizes the neurotoxins of 19 of the world's deadliest snakes

Snake venom protection by a cocktail of varespladib and broadly neutralizing human antibodies

Graphical abstract

Figure 1 In vivo and in vitro selection for broadly neutralizing antitoxin antibodies

The lack of effective Antivenoms in Africa

This has been a known issue for decades! Hopefully, African countries will step up and do more!

"In sub-Saharan Africa, a venomous snakebite is too often a death sentence: ~20,000 people in the region are killed each year, with rural populations especially impacted by lack of access to care and by severe antivenom shortages. 

But even getting an antivenom is no guarantee of survival, finds a deep dive by The Bureau of Investigative Journalism: 

• Diluted and fraudulent antivenoms have flooded the poorly regulated market. 
• Some corporations knowingly sell ineffective products—such as antivenoms made for Indian snakes, which are ineffective in Africa.

..."

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The New Snake Oil: Antivenoms That Are As Useless As Water (Caveat: I did not read this long article)

Universal antivenom for lethal snake toxins in different snakes from Asia and Africa developed by researchers

Good news! Taking the bite out of a snake bite! 

"The discovery of a powerful antibody that neutralizes a key neurotoxin common to four deadly snake species across Asia and Africa marks an important advance in the quest for a universal antivenom against the world’s ~200 venomous snakes; up to 138,000 people die each year from snake bites."

"Researchers have discovered a potent antibody that can neutralize a key type of neurotoxin produced by four different deadly snake species from South Asia, Southeast Asia, and Africa—a step toward an antivenom that could be used on any of the 200 or so dangerous venomous snakes throughout the world.

“We are wiping out a major subclass of neurotoxins here,” ... 

For one thing, snake venoms vary a lot between species, meaning treatment depends on which species has bitten you—which is not always known. Venoms can vary even within species ..."

From the editor's summary and abstract:

"Editor’s summary

Current strategies to treat snakebite envenoming rely on polyclonal antivenom derived from animals such as horses. Although these treatments can be life-saving, they can also result in serum sickness and anaphylaxis, and they require identification of the species of snake behind the bite. To address these limitations, Khalek et al. used a synthetic human antibody library to find and optimize a monoclonal antibody that could neutralize long-chain three-finger α-neurotoxins produced by the Elapidae family of snakes, which includes cobras, kraits, and mambas. The antibody was able to confer protection against envenoming in mice and functioned by mimicking the binding between the toxins and their receptors. This antibody and the approach used to find it represent a step forward on the path toward a universal, optimized antivenom. ...

Abstract

Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. Our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. Structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody–based universal antivenom to treat snakebite envenoming."

Universal antivenom for lethal snake toxins developed by researchers

Powerful new antivenom raises hopes for a universal solution to lethal snakebites Synthetic antibody neutralizes a key neurotoxin in different snakes from Asia and Africa

Johns Hopkins Bloomberg School of Public Health: Global Health NOW

Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins (open access)

Fig. 1. Cross-reactive anti–3FTx-L mAbs were isolated from a naive [???] library.