Abstract

Snakebite envenomation is a serious neglected tropical disease, and its management is often complicated by the diversity of snake venoms. In Asia, pit vipers of the Ovophis species complex are medically important venomous snakes whose venom properties have not been investigated in depth. This study characterized the venom proteomes of Ovophis convictus (West Malaysia), Ovophis tonkinensis (northern Vietnam, southern China), and Ovophis okinavensis (Okinawa, Japan) by applying liquid chromatography-tandem mass spectrometry, which detected a high abundance of snake venom serine proteases (SVSP, constituting 40–60% of total venom proteins), followed by phospholipases A2, snake venom metalloproteinases of mainly P-III class, L-amino acid oxidases, and toxins from other protein families which were less abundant. The venoms exhibited different procoagulant activities in human plasma, with potency decreasing from O. tonkinensis > O. okinavensis > O. convictus. The procoagulant nature of venom confirms that consumptive coagulopathy underlies the pathophysiology of Ovophis pit viper envenomation. The hetero-specific antivenoms Gloydius brevicaudus monovalent antivenom (GbMAV) and Trimeresurus albolabris monovalent antivenom (TaMAV) were immunoreactive toward the venoms, and cross-neutralized their procoagulant activities, albeit at variably limited efficacy. In the absence of species-specific antivenom, these hetero-specific antivenoms may be useful in treating coagulotoxic envenomation caused by the different snakes in their respective regions.

Highlights

  • Snakebite envenomation affects poor and marginalized populations in the tropics and subtropics most heavily, killing more than 100,000 people annually, and with three times as many suffer chronic complications [1,2,3,4]

  • Key Contribution: This study investigated the proteomes and coagulotoxicity of the Ovophis pit viper venom of three species from different geographical locales, elucidating the venom variability and pathophysiology of envenomation

  • This was followedof byeach and was heterogenous, with multiple protein bands of varying intensity distributed across a L-amino acid oxidase (LAAO), with protein abundances varying between 4.95% and 19.87% in the four snake wide range of molecular weights

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Summary

Introduction

Snakebite envenomation affects poor and marginalized populations in the tropics and subtropics most heavily, killing more than 100,000 people annually, and with three times as many suffer chronic complications [1,2,3,4]. In 2017, the World Health Organization formally recognized snakebite envenomation as one of the most neglected tropical diseases and called for a global strategy to overcome the problem [5]. This global health crisis remains to be adequately addressed with a comprehensive solution. The management of snakebite envenomation tends to be complicated by the great diversity and variable distribution of venomous snakes in different regions. Knowledge gaps in the identity, geographical distribution, and venom properties of specific species limit our understanding of the pathophysiology of envenomation, and this hinders appropriate treatment [3]. The supply and species coverage of antivenom products in most regions are inadequate, as antivenoms are produced by only a handful of domestic manufacturers in a few countries, with products indicated for selected important species in their respective countries [9]

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