Abstract
The World Health Organization (WHO) recently added snakebite envenoming to the priority list of Neglected Tropical Diseases (NTD). It is thought that ~75% of mortality following snakebite occurs outside the hospital setting, making the temporal gap between a bite and antivenom administration a major therapeutic challenge. Small molecule therapeutics (SMTs) have been proposed as potential prereferral treatments for snakebite to help address this gap. Herein, we discuss the characteristics, potential uses, and development of SMTs as potential treatments for snakebite envenomation. We focus on SMTs that are secretory phospholipase A2 (sPLA2) inhibitors with brief exploration of other potential drug targets on venom molecules.
Highlights
Snakebite envenomation is a neglected tropical disease that causes more than 100,000 deaths every year [1, 2]
Given their small molecular weight and charge, Small molecule therapeutics (SMTs) will generally have much higher volumes of distribution and tissue penetration than antivenom, allowing them to distribute within vulnerable tissues [26,27,28,29,30]
Because of its ubiquity and clinically significant effects, we focus on secreted phospholipase A2 (sPLA2) as a candidate for inhibition by SMTs [31, 40]
Summary
Snakebite envenomation is a neglected tropical disease that causes more than 100,000 deaths every year [1, 2]. Of the snakebites that are fatal, it is estimated that about 50-75% occur before victims can reach the hospital for antivenom treatment [3,4,5,6]. There is an urgent need for novel interventions to address the therapeutic and temporal gap between a bite and hospital-level care. Small molecule therapeutics (SMTs) have been proposed for initiating the treatment of snakebite in the prehospital environment and as adjuncts to antivenom therapy [7, 8]
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