The relationship between clinics and the venom of the causative Amazon pit viper (Bothrops atrox)

PLoS Negl Trop Dis. 2020 Jun 8;14(6):e0008299. doi: 10.1371/journal.pntd.0008299. eCollection 2020 Jun.

Abstract

Snake venoms are complex mixtures of proteins with toxic activities, with many distinct isoforms, affecting different physiological targets, comprised in a few protein families. It is currently accepted that this diversity in venom composition is an adaptive advantage for venom efficacy on a wide range of prey. However, on the other side, variability on isoforms expression has implications in the clinics of human victims of snakebites and in the efficacy of antivenoms. B. atrox snakes are responsible for most of the human accidents in Brazilian Amazon and the type and abundance of protein families on their venoms present individual variability. Thus, in this study we attempted to correlate the individual venom proteome of the snake brought to the hospital by the patient seeking for medical assistance with the clinical signs observed in the same patient. Individual variability was confirmed in venoms of the 14 snakes selected for the study. The abundance of each protein family was quite similar among the venom samples, while the isoforms composition was highly variable. Considering the protein families, the SVMP group presented the best correlation with bleeding disorders and edema. Considering individual isoforms, some isoforms of venom metalloproteinase (SVMP), C-type lectin-like toxins (CTL) and snake venom serine proteinases (SVSP) presented expression levels that with statistically significant positive correlation to signs and symptoms presented by the patients as bleeding disorders, edema, ecchymosis and blister formation. However, some unexpected data were also observed as the correlation between a CTL, CRISP or LAAO isoforms with blister formation, still to be confirmed with a larger number of samples. Although this is still a small number of patient samples, we were able to indicate that venom composition modulates clinical manifestations of snakebites, to confirm at the bedside the prominent role of SVMPs and to include new possible toxin candidates for the development of toxin inhibitors or to improve antivenom selectiveness, important actions for the next generation treatments of snakebites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antivenins
  • Bothrops*
  • Brazil
  • Crotalid Venoms / analysis*
  • Metalloproteases / analysis
  • Protein Isoforms / analysis
  • Proteome / analysis*
  • Proteomics
  • Serine Proteases / analysis*
  • Snake Bites / therapy

Substances

  • Antivenins
  • Crotalid Venoms
  • Protein Isoforms
  • Proteome
  • Metalloproteases
  • Serine Proteases

Grants and funding

This research was funded by Coordination for the Improvement of Higher Level Education Personnel-CAPES (Edital 2013-PROCAD-AuxPE 2992/2014), Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP (2013/07467-1 and 2018/25749-8) and Fundação de Amparo à Pesquisa do Estado do Amazonas-FAPEAM (PAPAC and PRO-ESTADO). AMMS (303958/2018-9), PSP (301778/2017-5), ML and WM are research fellows from CNPq. SNCG has a FAPESP post-doctoral fellowship (18/13108-8). JCCB and PFB receive CAPES doctoral scholarships. LAFS (2017/24546-3) and VMM have CAPES post-doctoral fellowship (18/13108-8). The funders had no role in study design, data collection and analysis, decision to publish, orpreparation of the manuscript.