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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 12; 11(12):e0006138.PN

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.

Authors+Show Affiliations

Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.Department of Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan. Liver Research Center, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan.Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Ministry of Health and Welfare, Taipei, Taiwan.Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Ministry of Health and Welfare, Taipei, Taiwan.Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29244815

Citation

Liu, Chien-Chun, et al. "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 Neglected Tropical Diseases, vol. 11, no. 12, 2017, pp. e0006138.
Liu CC, You CH, Wang PJ, et al. 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;11(12):e0006138.
Liu, C. C., You, C. H., Wang, P. J., Yu, J. S., Huang, G. J., Liu, C. H., Hsieh, W. C., & Lin, C. C. (2017). 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 Neglected Tropical Diseases, 11(12), e0006138. https://doi.org/10.1371/journal.pntd.0006138
Liu CC, et al. 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;11(12):e0006138. PubMed PMID: 29244815.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of the efficacy of Taiwanese freeze-dried neurotoxic antivenom against Naja kaouthia, Naja siamensis and Ophiophagus hannah through proteomics and animal model approaches. AU - Liu,Chien-Chun, AU - You,Chen-Hsien, AU - Wang,Po-Jung, AU - Yu,Jau-Song, AU - Huang,Guo-Jen, AU - Liu,Chien-Hsin, AU - Hsieh,Wen-Chin, AU - Lin,Chih-Chuan, Y1 - 2017/12/15/ PY - 2017/04/27/received PY - 2017/11/28/accepted PY - 2017/12/29/revised PY - 2017/12/16/pubmed PY - 2018/2/13/medline PY - 2017/12/16/entrez SP - e0006138 EP - e0006138 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 11 IS - 12 N2 - 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. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/29244815/Analysis_of_the_efficacy_of_Taiwanese_freeze_dried_neurotoxic_antivenom_against_Naja_kaouthia_Naja_siamensis_and_Ophiophagus_hannah_through_proteomics_and_animal_model_approaches_ L2 - http://dx.plos.org/10.1371/journal.pntd.0006138 DB - PRIME DP - Unbound Medicine ER -