Generation and In-planta expression of a recombinant single chain antibody with broad neutralization activity on Bothrops pauloensis snake venom

Int J Biol Macromol. 2020 Apr 15:149:1241-1251. doi: 10.1016/j.ijbiomac.2020.02.028. Epub 2020 Feb 5.

Abstract

The main systemic alterations present in bothropic envenomation are hemostasis disorders, for which the conventional treatment is based on animal-produced antiophidic sera. We have developed a neutralizing antibody against Bothrops pauloensis (B. pauloensis) venom, which is member of the genus most predominant in snakebite accidents in Brazil. Subsequently, we expressed this antibody in plants to evaluate its enzymatic and biological activities. The ability of single-chain variable fragment (scFv) molecules to inhibit fibrinogenolytic, azocaseinolytic, coagulant and hemorrhagic actions of snake venom metalloproteinases (SVMPs) contained in B. pauloensis venom was verified through proteolytic assays. The antibody neutralized the toxic effects of envenomation, particularly those related to systemic processes, by interacting with one of the predominant classes of metalloproteinases. This novel molecule is a potential tool with great antivenom potential and provides a biotechnological antidote to snake venom due to its broad neutralizing activity.

Keywords: Antivenom; Bothrops pauloensis; SVMP; Snake venom; scFv-Svmp1.

MeSH terms

  • Animals
  • Bothrops / metabolism*
  • Brazil / epidemiology
  • Caseins / metabolism
  • Chickens
  • Clone Cells
  • Cross Reactions / immunology
  • Fibrinogen / metabolism
  • Geography
  • Hemorrhage / pathology
  • Mice
  • Neutralization Tests*
  • Nicotiana / metabolism*
  • Protein Interaction Maps
  • Proteolysis
  • Recombinant Proteins / pharmacology*
  • Single-Chain Antibodies / isolation & purification
  • Single-Chain Antibodies / pharmacology*
  • Snake Bites / epidemiology
  • Snake Venoms / toxicity*

Substances

  • Caseins
  • Recombinant Proteins
  • Single-Chain Antibodies
  • Snake Venoms
  • azocasein
  • Fibrinogen