Studies carried out in mice have demonstrated that two permitted drugs — varespladib and marimastat — had been efficient in countering systemic and deadly results of Russell’s viper (Daboia russelii) venom both individually or together. The two drugs had been examined in opposition to Russell’s vipers venom sourced from totally different States throughout India. Russell’s vipers are chargeable for over half of India’s snakebite instances. The research led by Dr. Kartik Sunagar, Professor, Centre for Ecological Sciences at IISc, Bangalore, was revealed just lately within the journal Communications Medicine.
Dr. Sunagar and his staff are actually working with ICMR to design a human medical trial to take a look at the 2 drugs. “During the trial, the drugs will be used as an ancillary treatment to determine how effective they would be in treating snakebites,” he says. The management group management will obtain solely the antivenom however not the drugs.
Phospholipase A2 (PLA2), and Snake Venom Metalloproteinase (SVMPs) are two important parts of Russell’s viper snake venom. These toxins intrude with parts of the blood clotting cascade to induce anticoagulant and haemorrhagic results in people. While the varespladib drug inhibits PLA2, the marimastat drug inhibits SVMP.
Venom influencing elements
“In a 2021 study, we found differences in venoms of Russell’s vipers from across India depending on the biogeography where they were found. In a follow-up study, we showed that diet and development probably had a major influence in dictating the differences in the venom of Russell’s viper,” says Dr. Sunagar. “Another study published recently [April 2025] found that climatic conditions, such as temperature and rainfall, can also indirectly have a small effect on venom variation.”
“In the Western Ghats, characterised by heavy rainfall and dense forests, a rich variety of amphibians and arthropods thrive, providing snakes with a diverse diet. In contrast, arid regions experience limited rainfall and sparse plant cover, resulting in reduced diversity of prey available for snakes,” Dr. Sunagar says. “Temperature can also influence gene expression, though the extent to which this affects venom variation remains unclear. However, it is likely that temperature changes indirectly alter venoms by affecting the availability of prey composition in the region.”
Differences in venom
In the newest research, Russell’s viper venom from Punjab and Tamil Nadu exhibited the 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 drugs
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. In 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 in opposition to the venom with reasonable exercise, as seen in Madhya Pradesh, Rajasthan, and Goa.
Overall, the drugs 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 drugs 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. However, the therapeutic mixture of varespladib and marimastat almost fully inhibited these actions.
To replicate the real-world state of affairs and to take a look at the effectiveness of the drugs 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 in opposition to 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. In the case of venom from Karnataka, the Marimastat drug supplied solely 40% survival fee in opposition to the SVMP-rich venom on the finish of 24 hours even when the drug was administered quickly after venom injection.
In 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. But a therapeutic mixture of the 2 drugs conferred full safety from venom-induced lethality even when the drugs had been administered half-hour after venom injection.
According to 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 maybe equal to many hours delay in treating sufferers bitten by a Russell’s viper.
Designing a trial
Even in a single State, the snakes is likely to be producing a unique sort of toxin in several elements of the State. For occasion, 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, clinical trials must be conducted across various regions of India. Initially, we will begin the clinical trials in select regions and gradually expand them to cover most areas throughout the country. Once the trials are completed, we will determine which drug(s) are necessary for treatment in each specific region,” Dr. Sunagar says. The focused method will assist in treating sufferers with a single efficient drug or the drug mixture as an alternative of blindly utilizing the 2 drugs together throughout the nation and thereby decreasing dose effectiveness.
Published – June 18, 2025 12:43 pm IST
