How the venomous snake becomes less deadly

The Dutch newspaper AD interviewed Jeroen Kool about venomous snakes

01/18/2021 | 4:31 PM

(adapted from the Algemeen Dagblad news article of Hans van Zon who interviewed VU scientist Jeroen Kool)jeroenkool

How venomous snakes become less deadly: a pill and an antivenom can save tens of thousands of lives each year. A cheap pill that neutralizes the bite of a venomous snake. People in areas with the deadliest venomous snakes dream of this. Chemist Jeroen Kool is working on it.

He calls snake bites a very underestimated "tropical disease" and backs it up with numbers. “Snakebites kill at least 140,000 people every year, especially in poor countries. More than 400,000 people lose an arm or leg as a result, or get blind, " says chemist Dr. Jeroen Kool of the Vrije Universiteit Amsterdam (division of Bio-Analytical Chemistry within AIMMS). “So this is a serious topic, but unfortunately there has always been far too little attention. Former United Nations Secretary-General Kofi Annan once spoke of "the greatest health crisis of which you have never heard of."

Fortunately, that is starting to change. The problem is now on the top list of neglected tropical diseases (NTDs) of the World Health Organization (WHO). International conferences, including a conference at Naturalis in Leiden (2018), which was co-organized by Kool, ensures attention in the fight against snakebites. For example, together with colleagues from the Leuven University and the Liverpool School of Tropical Medicine, Kool’s research focusing on discovery and development of small molecular drugs for treating snakebite received a contribution of four million euros from the British Wellcome Trust.

After a bite from a viper or a cobra it seems logical to go to a hospital immediately. But people living in areas where the most dangerous venomous snakes live, especially in poor countries, sometimes first have to walk for several hours to get to the nearest hospital and then find out that the stock of antivenom is depleted. If they even make it to the first hospital… "When it comes to a venomous snake bite you have to act quickly and new drugs can help enormously" the chemist explains.

Thanks to existing drugs and drug candidates, one developed as anti-inflammatory drug candidate and one for cancer treatment, combined they are working as an effective alternative to antivenoms. These antivenoms have many drawbacks: they are expensive, have to be injected in a hospital, often have very dangerous immunological side effects, and only work against venom from one or a few specific snake species. "In many geographical areas of the world if you don't know which snake bit you, doctors don't know which antivenom to use," says Jeroen Kool. His alternative: an affordable pill that can be taken anywhere, anytime." The fact that we can rely on already developed drugs or drug candidates for their development into snakebite treatments can save huge amounts of money on clinical studies, as these already have been done for these compounds" Kool explains.

“Snake venom has different families of toxic enzymes that destroy the body in their own way. Using these candidate drugs, we have shown that they are effective against venom from different snake families. These include the "vipera" (rattlesnakes and vipers, including the saw-scaled viper, one of the deadliest snakes on Earth) and the "elapids" (e.g. cobras and mambas). “The venoms from many vipera interfere with the cardiovascular system and can cause life-threatening hemotoxicity. Venoms from cobras and mambas on the other hand mainly work with neurotoxins. Your muscles paralyze, your lung muscles stop working and then it ends quickly," says Kool. The research now focuses mainly on the vipera that live in South America, Africa, India and Southeast Asia. “Our compounds worked very effectively on medically relevant vipera from all these regions."

The first small molecular drug we tested is one used for heavy metal poisoning (i.e. DMPS). It is a metal chelator that traps heavy metals such as lead, cadmium and some other metal ions that enter the body after heavy metal poisoning. Why this medicine? Because many of the dangerous enzymes in snake venoms have one thing in common - they contain zinc (i.e. they are metalloproteases which coordinate zinc in their active site). By chelating the zinc ions, these proteases are neutralized. And this works in vivo by administering orally active DMPS.

If these small molecular drugs and drug candidates can be repurposed into snakebite treatments, most probably antivenoms will not disappear. The strength is to expected in the combination. Pills with orally active small molecular drugs can immediately serve as on-site first aid directly after a snakebite, after which a victim has more time to go to a hospital for subsequent antivenom treatment.

Currently a clinical trial is in preparation and is anticipated to be conducted in two African countries. But it is very difficult to get pharmaceutical companies interested. The majority of the victims fall in very poor countries, where there is little to be earned for a pharmaceutical company. If the results of the first clinical studies are promising, we can turn to governments and investors such as the Bill and Melinda Gates foundation to ask for funding for further development.

You can find the article in Het Algemeen Dagblad (zaterdag editie van 16 januari 2021) here.

echis carinatus2

Echis carinatus (saw scale viper) made by Wolfgang Wuster