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The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India

Snake envenoming afflicts the Indian subcontinent with the highest rates of mortality (47,000) and morbidity globally. The only effective treatment for snakebites is the administration of antivenom, which is produced by the hyperimmunisation of equines. Commercial Indian antivenoms, however, have be...

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Autores principales: Attarde, Saurabh, Iyer, Ashwin, Khochare, Suyog, Shaligram, Umesh, Vikharankar, Mayur, Sunagar, Kartik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950585/
https://www.ncbi.nlm.nih.gov/pubmed/35324665
http://dx.doi.org/10.3390/toxins14030168
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author Attarde, Saurabh
Iyer, Ashwin
Khochare, Suyog
Shaligram, Umesh
Vikharankar, Mayur
Sunagar, Kartik
author_facet Attarde, Saurabh
Iyer, Ashwin
Khochare, Suyog
Shaligram, Umesh
Vikharankar, Mayur
Sunagar, Kartik
author_sort Attarde, Saurabh
collection PubMed
description Snake envenoming afflicts the Indian subcontinent with the highest rates of mortality (47,000) and morbidity globally. The only effective treatment for snakebites is the administration of antivenom, which is produced by the hyperimmunisation of equines. Commercial Indian antivenoms, however, have been shown to exhibit a poor preclinical performance in neutralising venom, as a result of inter- and intrapopulation snake venom variation. Additionally, their poor dose effectiveness necessitates the administration of larger volumes of antivenom for treatment, leading to several harmful side effects in snakebite victims, including serum sickness and fatal anaphylaxis. In this study, we employed chromatographic purification to enhance the dose efficacy of commercial Indian antivenoms. The efficacy of this ‘second-generation’ antivenom was comparatively evaluated against six other marketed antivenoms using a number of in vitro and in vivo preclinical assays, which revealed its superior venom recognition capability. Enhanced purity also resulted in significant improvements in dose effectiveness, as the ‘second-generation’ antivenom exhibited a 3 to 4.5 times increased venom neutralisation potential. Furthermore, preclinical assays revealed the increased effectiveness of the ‘second-generation’ antivenom in countering morbid effects inflicted by the ‘big four’ Indian snakes. Thus, we demonstrate the role of simpler purification steps in significantly enhancing the effectiveness of snakebite therapy in regions that are most affected by snakebites.
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spelling pubmed-89505852022-03-26 The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India Attarde, Saurabh Iyer, Ashwin Khochare, Suyog Shaligram, Umesh Vikharankar, Mayur Sunagar, Kartik Toxins (Basel) Article Snake envenoming afflicts the Indian subcontinent with the highest rates of mortality (47,000) and morbidity globally. The only effective treatment for snakebites is the administration of antivenom, which is produced by the hyperimmunisation of equines. Commercial Indian antivenoms, however, have been shown to exhibit a poor preclinical performance in neutralising venom, as a result of inter- and intrapopulation snake venom variation. Additionally, their poor dose effectiveness necessitates the administration of larger volumes of antivenom for treatment, leading to several harmful side effects in snakebite victims, including serum sickness and fatal anaphylaxis. In this study, we employed chromatographic purification to enhance the dose efficacy of commercial Indian antivenoms. The efficacy of this ‘second-generation’ antivenom was comparatively evaluated against six other marketed antivenoms using a number of in vitro and in vivo preclinical assays, which revealed its superior venom recognition capability. Enhanced purity also resulted in significant improvements in dose effectiveness, as the ‘second-generation’ antivenom exhibited a 3 to 4.5 times increased venom neutralisation potential. Furthermore, preclinical assays revealed the increased effectiveness of the ‘second-generation’ antivenom in countering morbid effects inflicted by the ‘big four’ Indian snakes. Thus, we demonstrate the role of simpler purification steps in significantly enhancing the effectiveness of snakebite therapy in regions that are most affected by snakebites. MDPI 2022-02-24 /pmc/articles/PMC8950585/ /pubmed/35324665 http://dx.doi.org/10.3390/toxins14030168 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Attarde, Saurabh
Iyer, Ashwin
Khochare, Suyog
Shaligram, Umesh
Vikharankar, Mayur
Sunagar, Kartik
The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India
title The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India
title_full The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India
title_fullStr The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India
title_full_unstemmed The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India
title_short The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India
title_sort preclinical evaluation of a second-generation antivenom for treating snake envenoming in india
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950585/
https://www.ncbi.nlm.nih.gov/pubmed/35324665
http://dx.doi.org/10.3390/toxins14030168
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