Rudresha Gotravalli V, Khochare Suyog, Casewell Nicholas R, Sunagar Kartik
Evolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bengaluru, Karnataka, India.
Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, UK.
Commun Med (Lond). 2025 Jun 10;5(1):226. doi: 10.1038/s43856-025-00900-z.
Snakebites are problematic in many developing regions, including India, where over half of global snakebite deaths occur. Antivenoms are currently the only licensed treatment for snakebites. However, their use causes several challenges, most notably geographical limitations in efficacy and adverse side effects. Therefore, therapeutic alternatives are urgently needed. Recently, several studies have evaluated small molecule inhibitors (SMIs) and highlighted their promise as safe and effective alternatives to antivenoms. We investigate their potential use against Indian snakes, particularly Russell's viper (Daboia russelii), responsible for over half of India's snakebite cases.
Here, we explored the effectiveness of two phase-2-approved SMIs in countering the diverse and variable toxicities of D. russelii from across India.
The phospholipase inhibitor varespladib and the metalloproteinase inhibitor marimastat, individually or in combination, effectively counter the toxicities of D. russelii venoms in vitro. Specific drug efficacy varies across geographic regions. These SMIs and their combination prevent lethality caused by the pan-Indian D. russelii, even in rescue experiments where treatment is delayed, in mice.
Our findings support the potential use of SMIs as effective, affordable, and accessible future therapies for treating bites from the world's most medically important snake species.
蛇咬伤在包括印度在内的许多发展中地区都是个问题，全球超过一半的蛇咬伤死亡事件发生在印度。抗蛇毒血清是目前唯一经许可用于治疗蛇咬伤的药物。然而，其使用带来了诸多挑战，最显著的是疗效的地理局限性和不良副作用。因此，迫切需要治疗替代方案。最近，多项研究评估了小分子抑制剂（SMIs），并强调了它们作为抗蛇毒血清安全有效替代品的前景。我们研究了它们针对印度蛇类，特别是对印度一半以上蛇咬伤病例负有责任的罗素蝰蛇（Daboia russelii）的潜在用途。
在此，我们探究了两种已获二期批准的小分子抑制剂在对抗来自印度各地的罗素蝰蛇的多样且多变毒性方面的有效性。
磷脂酶抑制剂伐瑞普拉迪布和金属蛋白酶抑制剂马立马司他单独或联合使用，在体外均能有效对抗罗素蝰蛇毒液的毒性。具体药物疗效因地理区域而异。这些小分子抑制剂及其组合可预防全印度罗素蝰蛇造成的致死性，即使在小鼠的救援实验中治疗延迟的情况下也是如此。
我们的研究结果支持小分子抑制剂作为治疗世界上医学上最重要蛇种咬伤的有效、经济且可及的未来疗法的潜在用途。
