Ontogenetic variation in coagulotoxic activity and antivenom efficacy of Central American pit viper venoms (Cerrophidion, Metlapilcoatlus, Ophryacus and Porthidium)

Abstract

Ontogenetic variation in venom activity and composition has been documented across several pit viper genera, but these toxicological variations are poorly understood in Cerrophidion, Metlapilcoatlus, Ophryacus, and Porthidum. This study investigated ontogenetic changes in coagulotoxic venom activity across adult and juvenile specimens of Cerrophidion petlalcalensis, Metlapilcoatlus olmec, M. nummifer, Ophryacus undulatus, Porthidium ophryomegas, and P. yucatanicum. Adult C. petlalcalensis, M. olmec, and M. nummifer displayed potent thrombin-like activity, resulting in a pseudo-procoagulant action whereby the venoms directly acted upon fibrinogen to produce weak, unstable fibrin clots that rapidly break down, thereby contributing to anticoagulant pathophysiological effects by depleting fibrinogen levels. In contrast, their juvenile counterparts showed either weaker or no such activity. Ophryacus undulatus displayed an ontogenetic shift in anticoagulant targets, where adults inhibited clotting factors and juveniles did not. The anticoagulant target for juvenile O. undulatus remains unknown, with this study ruling out fibrinogen degradation, factor inhibition and phospholipid degradation. Both adult and juvenile P. ophryomegas and P. yucatanicum exhibited potent anticoagulant effects through fibrinogen degradation and factor inhibition. These species exhibited previously undocumented factor VIIa inhibition, a mechanism not previously reported in viperid venoms. The regionally available PoliVal-ICP polyvalent antivenom effectively cross-neutralized the pseudo-procoagulant activities of Cerrophidion and Metlapilcoatlus, across both life stages tested. These findings reveal significant ontogenetic variation in venom activity and antivenom efficacy, with implications for both clinical management of snakebite and our understanding of venom evolution in these species.