Anticoagulant Micrurus venoms: Targets and neutralization

Area of Science:

• Biochemistry
• Toxicology
• Pharmacology

Background:

• Snakebite envenoming is a significant global health issue, classified as a neglected tropical disease.
• Current antivenom treatments face challenges in supply and accessibility, particularly in resource-limited settings.
• The anticoagulant properties of Micrurus (coral snake) venoms remain largely uncharacterized.

Purpose of the Study:

• To investigate the anticoagulant effects of Micrurus genus venoms.
• To evaluate the efficacy of coral snake antivenom (Coralmyn) and varespladib in counteracting these anticoagulant properties.
• To explore varespladib as a potential alternative treatment for snakebite envenoming.

Main Methods:

• In vitro assessment of venom anticoagulant activity.
• Testing the neutralizing capacity of Coralmyn and varespladib against venom-induced anticoagulation.
• Analysis of venom composition regarding phospholipase A2 (PLA2) and three-finger toxin families.

Main Results:

• Micrurus venoms displayed variable anticoagulant potency, with M. laticollaris showing pronounced effects, likely by interfering with the prothrombinase complex.
• Coral snake antivenom (Coralmyn) showed limited efficacy, only ameliorating effects from M. ibiboboca venom.
• Varespladib completely abolished the anticoagulant activity of all tested venoms, irrespective of toxin family expression.

Conclusions:

• Varespladib demonstrates broad-spectrum efficacy against venom-induced anticoagulation, suggesting its potential as a versatile snakebite therapeutic.
• The logistical advantages of varespladib, including temperature stability and oral availability, position it as a favorable alternative to conventional antivenoms.
• Further research into varespladib could significantly alleviate the global burden of snakebite injuries and fatalities.