Phenotypic dichotomy in Crotalus durissus ruruima venom and potential consequence

Background The phenotypic polymorphism in rattlesnake venoms has been thoroughly documented, showing a dichotomy between haemorrhagic (Type I) and neurotoxic (Type II) venoms. In South America, the Type II phenotype is predominant; however, evidence exists of Type I haemorrhagic venoms in C. d. ruruima, raising questions about the efficacy of the Crotalus antivenom prepared for the Type II phenotype in treating Crotalus Type I snakebite patients, for whom the administration of Bothrops-Crotalus antivenom has been proposed. Methodology/Principal Findings This study characterises the dichotomy of C. d. ruruima venom based on the structure of isoforms differentially expressed in Type I and Type II venoms, the biological activities of each phenotype, and the implications for the clinical management of snakebites in Northern Brazil. Four toxins were differentially expressed in Type I and Type II venoms: two PIII-class SVMPs, which were highly expressed in Type I venoms and associated with proteolytic and haemorrhagic activity, and two PLA2s, corresponding to Crotoxin A and B chains, identified in Type II venoms and associated with increased phospholipase A2, myotoxic activities, and heightened lethality. The structure of Crotoxin chains was well conserved compared to C. d. terrificus crotoxin. However, compared to Bothropasin, the SVMP sequences exhibited several substitutions in functional and immunoreactive regions, resulting in low haemorrhagic activity and slight reactivity/neutralisation by Bothrops antivenom. In opposition, Crotalus antivenom reacted with high antibody titres and neutralised all activities of both venom subtypes, except the low haemorrhagic activity induced by Type I venoms. Conclusions/Significance The efficacy of Bothrops antivenom in incidents involving snakes of the Type I phenotype remains uncertain, and we advocate for an urgent prospective study in Roraima to assess the outcomes and benefits for patients receiving either Bothrops-Crotalus or solely Crotalus antivenoms following rattlesnake bites. Meanwhile, administering Bothrops-Crotalus antivenom could be warranted. However, it is crucial to remain aware of the issues of injecting heterologous Bothrops antibodies with limited efficacy in treating Crotalus snakebite patients.