Dagestan blunt-nosed viper, (Dwigubsky, 1832), venom. Venomics, antivenomics, and neutralization assays of the lethal and toxic venom activities by anti- and anti- antivenoms.

We have applied a combination of venomics, neutralization assays, and third-generation antivenomics analysis to assess the preclinical efficacy of the monospecific anti- (anti-Mlt) antivenom manufactured by Uzbiopharm® (Uzbekistan) and the monospecific anti- antivenom from Microgen® (Russia) against the venom of Dagestan blunt-nosed viper, (Mlo). Despite their low content of homologous (anti-Mlt, 5-10%) or para-specific (anti-Vbb, 4-9%) F(ab') antibody fragments against venom toxins, both antivenoms efficiently recognized most components of the complex venom proteome's arsenal, which is made up of toxins derived from 11 different gene families and neutralized, albeit at different doses, key toxic effects of venom, i.e., lethal and hemorrhagic effects in a murine model, and phospholipase A, proteolytic and coagulant activities. The calculated lethality neutralization potencies for Uzbiopharm® anti-Mlt and anti-Vbb Microgen® antivenoms were 1.46 and 1.77 mg/mL, indicating that 1 mL of Uzbiopharm® and Microgen® antivenoms may protect mice from 41 to 50 LDs of Mlo venom, respectively. The remarkable degree of conservation of immunogenic determinants between species of the clades of European and Oriental viper, which evolved geographically segregated since the early Miocene, suggests an eventual window of opportunity for the treatment of envenomings by Eurasian snakes. Clearly, the rational use of heterologous antivenoms requires establishing their para-specificity landscapes. This paper illustrates the analytical power of combining and preclinical quantitative assays toward this goal.