Two existing drugs offer hope to cure Russell’s viper bites

Research carried out in mice have demonstrated that two authorised medicine — varespladib and marimastat — had been efficient in countering systemic and deadly results of Russell’s viper (Daboia russelii) venom both individually or together. The 2 medicine had been examined towards Russell’s vipers venom sourced from totally different States throughout India. Russell’s vipers are answerable for over half of India’s snakebite circumstances. The examine led by Dr. Kartik Sunagar, Professor, Centre for Ecological Sciences at IISc, Bangalore, was revealed just lately within the journal Communications Medication.

Dr. Sunagar and his crew at the moment are working with ICMR to design a human medical trial to check the 2 medicine. “In the course of the trial, the medicine might be used as an ancillary therapy to find out how efficient they’d be in treating snakebites,” he says. The management group management will obtain solely the antivenom however not the medicine.

Phospholipase A₂ (PLA₂), and Snake Venom Metalloproteinase (SVMPs) are two primary parts of Russell’s viper snake venom. These toxins intervene with parts of the blood clotting cascade to induce anticoagulant and haemorrhagic results in people. Whereas the varespladib drug inhibits PLA₂, the marimastat drug inhibits SVMP. 

Venom influencing components

“In a 2021 examine, we discovered variations in venoms of Russell’s vipers from throughout India relying on the biogeography the place they had been discovered. In a follow-up examine, we confirmed that weight loss plan and growth most likely had a serious affect in dictating the variations within the venom of Russell’s viper,” says Dr. Sunagar. “One other examine revealed just lately [April 2025] discovered that weather conditions, comparable to temperature and rainfall, may also not directly have a small impact on venom variation.”

“Within the Western Ghats, characterised by heavy rainfall and dense forests, a wealthy number of amphibians and arthropods thrive, offering snakes with a various weight loss plan. In distinction, arid areas expertise restricted rainfall and sparse plant cowl, leading to decreased variety of prey out there for snakes,” Dr. Sunagar says. “Temperature may also affect gene expression, although the extent to which this impacts venom variation stays unclear. Nevertheless, it’s doubtless that temperature adjustments not directly alter venoms by affecting the provision of prey composition within the area.”

Variations in venom

Within the newest examine, Russell’s viper venom from Punjab and Tamil Nadu exhibited the very best PLA₂ exercise, adopted by different areas — Kerala, Maharashtra, Goa, and Madhya Pradesh. Russell’s viper snake venom from all different areas exhibited minimal PLA₂ exercise. Proteinase exercise was highest in Karnataka adopted by the Rajasthan, Madhya Pradesh, Goa, and Andhra Pradesh areas. In distinction, venom from Tamil Nadu exhibited little to no exercise, whereas venom samples from different areas exhibited modest proteolytic exercise.

Effectiveness of medicine

The PLA₂ inhibitor varespladib was discovered to neutralise even the excessive PLA₂ exercise of the venom present in Tamil Nadu and Punjab. The varespladib drug successfully inhibited the modest PLA2 exercise of the venom from different Indian areas. Within the case of the matrix metalloprotease-inhibiting drug, marimastat, the drug successfully inhibited the venom in a concentration-dependent method. The drug was efficient even when the proteolytic exercise was excessive, as seen in Karnataka. As anticipated, the drug exhibited extremely potent inhibitory results towards the venom with reasonable exercise, as seen in Madhya Pradesh, Rajasthan, and Goa. 

General, the medicine varespladib and marimastat when used individually or in a therapeutic drug mixture had been discovered to be very efficient in decreasing venom-induced cytotoxicity, venom-induced coagulopathy, and fibrinogenolysis. When used individually, the medicine had been efficient in decreasing the venom-induced cytotoxicity by snake populations from some areas whereas being much less efficient within the case of venom from another areas. Nevertheless, the therapeutic mixture of varespladib and marimastat practically fully inhibited these actions.

To copy the real-world state of affairs and to check the effectiveness of the medicine after the venom problem, the researchers administered the drug half-hour after venom supply.

Rescue experiments involving PLA₂-rich snake venom from Punjab revealed that the varespladib drug conferred full safety towards venom-induced lethality even when the drug was administered half-hour after venom injection. In distinction, marimastat was ineffective in rescue experiments even when the drug was administered quickly after venom supply. Within the case of venom from Karnataka, the Marimastat drug supplied solely 40% survival fee towards the SVMP-rich venom on the finish of 24 hours even when the drug was administered quickly after venom injection.

Within the case of venom from Madhya Pradesh, which is wealthy in each SVMP and PLA₂, varespladib and marimastat individually supplied solely 60% and 40% safety, respectively, when dosed instantly after venom problem. However a therapeutic mixture of the 2 medicine conferred full safety from venom-induced lethality even when the medicine had been administered half-hour after venom injection.

In line with Dr. Sunagar, because the physique measurement of mice is extraordinarily small, the place they weigh between 18-22 grams, half-hour delay in administering the drug is probably equal to many hours delay in treating sufferers bitten by a Russell’s viper.

Designing a trial

Even in a single State, the snakes could be producing a unique kind of toxin in several components of the State. As an illustration, in Karnataka, one drug is efficient within the southern a part of the State, whereas the opposite drug is efficient within the northern a part of the State. “Given this stark variation in venoms, medical trials have to be carried out throughout varied areas of India. Initially, we are going to start the medical trials in choose areas and step by step increase them to cowl most areas all through the nation. As soon as the trials are accomplished, we are going to decide which drug(s) are obligatory for therapy in every particular area,” Dr. Sunagar says. The focused method will assist in treating sufferers with a single efficient drug or the drug mixture as a substitute of blindly utilizing the 2 medicine together throughout the nation and thereby decreasing dose effectiveness.