Analysis of the efficacy of Taiwanese freeze-dried neurotoxic antivenom against Naja kaouthia, Naja siamensis and Ophiophagus hannah through proteomics and animal model approaches

PLoS Negl Trop Dis. 2017 Dec 15;11(12):e0006138. doi: 10.1371/journal.pntd.0006138. eCollection 2017 Dec.

Abstract

In Southeast Asia, envenoming resulting from cobra snakebites is an important public health issue in many regions, and antivenom therapy is the standard treatment for the snakebite. Because these cobras share a close evolutionary history, the amino acid sequences of major venom components in different snakes are very similar. Therefore, either monovalent or polyvalent antivenoms may offer paraspecific protection against envenomation of humans by several different snakes. In Taiwan, a bivalent antivenom-freeze-dried neurotoxic antivenom (FNAV)-against Bungarus multicinctus and Naja atra is available. However, whether this antivenom is also capable of neutralizing the venom of other species of snakes is not known. Here, to expand the clinical application of Taiwanese FNAV, we used an animal model to evaluate the neutralizing ability of FNAV against the venoms of three common snakes in Southeast Asia, including two 'true' cobras Naja kaouthia (Thailand) and Naja siamensis (Thailand), and the king cobra Ophiophagus hannah (Indonesia). We further applied mass spectrometry (MS)-based proteomic techniques to characterize venom proteomes and identify FNAV-recognizable antigens in the venoms of these Asian snakes. Neutralization assays in a mouse model showed that FNAV effectively neutralized the lethality of N. kaouthia and N. siamensis venoms, but not O. hannah venom. MS-based venom protein identification results further revealed that FNAV strongly recognized three-finger toxin and phospholipase A2, the major protein components of N. kaouthia and N. siamensis venoms. The characterization of venom proteomes and identification of FNAV-recognizable venom antigens may help researchers to further develop more effective antivenom designed to block the toxicity of dominant toxic proteins, with the ultimate goal of achieving broadly therapeutic effects against these cobra snakebites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidotes / chemistry
  • Antidotes / pharmacology*
  • Antivenins / chemistry
  • Antivenins / pharmacology*
  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid
  • Disease Models, Animal
  • Elapid Venoms / chemistry*
  • Elapid Venoms / poisoning
  • Freeze Drying
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutralization Tests
  • Proteome*
  • Snake Bites / drug therapy*
  • Taiwan
  • Tandem Mass Spectrometry

Substances

  • Antidotes
  • Antivenins
  • Elapid Venoms
  • Proteome

Grants and funding

This work was supported by the Ministry of Education, Taiwan (grant EMRPD1F0031 and EMRPD1G0021 to Chang Gung University), by the Ministry of Science and Technology, Taiwan (grants MOST 104-2325-B-182-003 and 105-2325-B-182-001 to JSY); and by Chang Gung Memorial Hospital, Taiwan (grants CMRPG3F0241-242 to CCLin, CIRPD3B0013, CRRPD1F0051, CMRPD190364, CLRPD190016 and BMRP208 to JSY) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.