Two small molecule inhibitors hold possible cure for Russell’s viper bites

Russell’s viper causes more than 50% of human casualties due to snakebites in India.

Hubballi: Varespladib and Marimastat, two of the small molecule inhibitors (SMIs), hold a possible solution to treat Russell’s viper snake
bites.

Russell’s viper causes more than 50 per cent of human casualties due to snakebites in India. Scientists say this could lead to creating orally active formulations.

SMIs are currently used in treating cancer and heart-related diseases. A study by scientists of The Evolutionary Venomics Lab, Bengaluru, has found that these two repurposed drugs, used individually or in combination, effectively neutralised the venom and fully protected the mice from lethal venom effects, even when administration was
delayed.

This study was published in Nature Communications Medicine and was authored by Rudresha G V, Suyog Khochare, Nicholas Casewell and Kartik
Sunagar.

The lab will be teaming up with Indian Council of Medical Research to take these drugs into human clinical trials.

If everything goes as per plan, it could revolutionise treatment of snakebites.

India, on an average, reports 58,000 human deaths due to snakebites and nearly three times more people get disabled or amputated.

“There are several advantages of developing anti-venom doses using SMIs. They have a broad spectrum of effectivity, little to no adverse reactions, greater stability, cost-effectiveness and most importantly, the possibility of creating orally active formulations,” says
Kartik. 

Currently antivenom vials, produced after introducing snake venom into another animal body and extracting antibodies, is the only scientifically advocated treatment for
snakebite.

Despite its life-saving efficacy, antivenoms exhibit several important shortcomings, including limited potency and cross-snake species efficacy, high incidences of adverse reactions, inability to counter snakebite-induced morbidity, cost of production and necessity to be delivered intravenously in a clinical setting, he says. 

SMIs, many of which are already approved for clinical use or have previously entered clinical trials, could offer a safer and more effective alternative to antivenom treatment, he
adds.

The other advantages of developing SMIs are, unlike a few antivenom formulations, they don’t need cold storage or other infrastructure that are hard to provide in rural areas. 

They can be safely taken without clinical assistance and can be produced without harming other animals.

During studies, the team found that administration of Varespladib and Marimastat offered complete protection against the systemic and lethal effects of viper’s
venom.

“Usually, when a viper bites there is high possibility of tissues getting damaged, resulting in amputation of that part. During our study on mice, we found that this adverse impact was prevented even after delayed administered,” he says. 

If during human trials, same results are achieved, it will be a game changer, Kartik adds.

As of now, the team has confirmed the efficacy of the two SMIs only on viper, the world’s most medically important snake species. Soon, they will be testing against other venomous
snakes.