Analysis of the efficacy of Taiwanese freeze-dried neurotoxic antivenom against Naja kaouthia, Naja siamensis and Ophiophagus hannah through proteomics and animal model approaches
| العنوان: | Analysis of the efficacy of Taiwanese freeze-dried neurotoxic antivenom against Naja kaouthia, Naja siamensis and Ophiophagus hannah through proteomics and animal model approaches |
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| المؤلفون: | Wen-Chin Hsieh, Chih-Chuan Lin, Po-Jung Wang, Jau-Song Yu, Guo-Jen Huang, Chien-Chun Liu, Chen-Hsien You, Chien-Hsin Liu |
| المصدر: | PLoS Neglected Tropical Diseases, Vol 11, Iss 12, p e0006138 (2017) PLoS Neglected Tropical Diseases |
| بيانات النشر: | Public Library of Science (PLoS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Proteome, Proteomes, Physiology, Antidotes, Antivenom, Snake Bites, Toxicology, Pathology and Laboratory Medicine, Biochemistry, Mice, Tandem Mass Spectrometry, Immune Physiology, Medicine and Health Sciences, Toxins, Snakebite, Chromatography, High Pressure Liquid, Liquid Chromatography, Cobras, Immune System Proteins, biology, Traditional medicine, Antivenins, Elapid Venoms, lcsh:Public aspects of medicine, Chromatographic Techniques, Eukaryota, Snakes, Squamates, Infectious Diseases, Vertebrates, Research Article, Neglected Tropical Diseases, lcsh:Arctic medicine. Tropical medicine, King cobra, lcsh:RC955-962, Naja, Toxic Agents, Immunology, Taiwan, Research and Analysis Methods, complex mixtures, 03 medical and health sciences, Neutralization Tests, Animals, Humans, Naja kaouthia, Antigens, Envenomation, Naja siamensis, Venoms, Organisms, Public Health, Environmental and Occupational Health, Biology and Life Sciences, Reptiles, Proteins, lcsh:RA1-1270, Venom Protein, Tropical Diseases, biology.organism_classification, High Performance Liquid Chromatography, Mice, Inbred C57BL, Disease Models, Animal, Freeze Drying, 030104 developmental biology, Amniotes, Chromatography, Liquid |
| الوصف: | 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. Author summary Cobra envenomation is a public health issue in Southeast Asia. Currently, antivenom therapy is the standard treatment for snakebite. However, antivenoms are not available in many rural countries and communities or have only limited effectiveness. Taiwan has wealth of experience in producing antivenoms, including the bivalent freeze-dried neurotoxic antivenom (FNAV), which is raised against venom proteins from Bungarus multicinctus and Naja atra. Our results showed that FNAV effectively neutralized the lethality of Naja kaouthia(Thailand) and Naja siamensis (Thailand) venoms, but not Ophiophagus hannah (Indonesia) venom, in an animal model. We further characterized the venom proteome profiles of the four cobras and identified three abundant proteins—neurotoxin, cytotoxin and phospholipase A2—in the venom of N. atra, N. kaouthia and N. siamensisas the major antigens recognized by FNAV. In contrast, we found that β-cardiotoxin and phospholipase A2, common toxin proteins in all king cobra venom samples, are weakly or not recognized by FNAV. Our data provide evidence suggesting the potential use of Taiwan’s FNAV to treat envenomation by other cobra species (N. kaouthia and N. siamensis) in Southeast Asia. Moreover, our findings support the previous recommendation and current experimental approach that major cobra toxins are used as antigens to generate more efficient antivenoms than those currently available. |
| اللغة: | English |
| تدمد: | 1935-2735 1935-2727 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7ad4013fd3a6db8c30d7f37f5f0ba888 http://europepmc.org/articles/PMC5747474?pdf=render |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7ad4013fd3a6db8c30d7f37f5f0ba888 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19352735 19352727 |
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