Potent antidote to Cobra and Krait venom toxins

News Excerpt:

According to a 2020 world health organisation report, the mortality burden is especially higher in low and middle-income countries in Africa and Asia, with India alone at a staggering average of 58,000 deaths in a year.

  • Venom from snake bites leads to more than 100,000 deaths every year, with around 400,000 people left permanently disabled.

Various types of venoms:

  • Venoms of snakes in India are so diverse that the same antivenom can’t neutralise venoms of the same species across regions.
  • Even in the same geographical location, antivenom can only neutralise some venoms and not others.

Screening billions of antibodies:

  • The scientists focused on three-finger toxins (3FTxs) — one of the most abundant and lethal ingredients in elapid venoms
    • Elapids are a major medically relevant family of snakes that include cobras, kraits, and mambas.
  • The scientists narrowed their focus on α-neurotoxins, a class of 3FTxs that target human nerve and muscle cell receptors. 
    • These toxins prevent the receptors from responding to acetylcholine, a neurotransmitter involved in carrying messages from the neurons to the muscles, leading to paralysis, an inability to breathe, and eventually death.
  • Scientists tested the antibodies in vitro in human cells to see which of them could best neutralise the toxins. This step brought them to an antibody they dubbed 95Mat5.
    • They tested 95Mat5 in vivo in mice to see if this broadly neutralising antibody could help protect against lethal doses of α-bungarotoxin, the 3FTx-L in the highly venomous many-banded kraits.
    • They found 95Mat5 worked well against all the snake venoms, with the only exception being the king cobras’ venom, where the antibody delayed but could not prevent death.

Universal solution:

  • In the current study, the scientists found one reason why their antibody worked so well against their toxins of interest. 
    • The crystal structures of their antibody 96Mat5 and 3FTx-L variants revealed that the antibody bound the toxin exactly where it would have bound its target receptor in human nerve and muscle cells. 
    • By mimicking the receptor-toxin interaction, the antibody could whisk the toxins away from the receptors and prevent them from exerting their deadly effects.
  • The current antibody works well against a specific kind of toxin present in the venom of many dangerous snakes. Still, it is a small first step towards a universal antivenom. 
  • The scientists said they are keen on discovering specific antibodies like these against toxins in other snake venoms as well, like in vipers.

Trends in snakebite deaths in India from 2000 to 2019:

  • According to the World Health Organization (WHO), India had 1.2 million snakebite deaths (average 58,000/year) from 2000 to 2019. 
  • Nearly half occurred at ages 30–69 years and over a quarter in children < 15 years. 
    • Most occurred at home in the rural areas. 
    • About 70% occurred in eight higher burden states and half during the rainy season and at low altitudes. 
  • The risk of an Indian dying from snake bite before age 70 is about 1 in 250, but notably higher in some areas. 
  • More crudely, WHO estimated 1.11 - 1.77 million bites in 2015, of which 70% showed symptoms of envenomation. 
  • Bites by venomous snakes cause acute medical emergencies involving shock, paralysis, haemorrhage, acute kidney injury and severe local tissue destruction that leads to permanent disability.
  • Prevention and treatment strategies might substantially reduce snakebite mortality in India.
  • WHO aims to halve global snakebite deaths by 2030 will require substantial progress in India.

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