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An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms

Introduction: Most elapid snakes produce venoms that contain alpha-neurotoxins (a-NTXs), which are proteins that cause post-synaptic blockade and paralysis in snakebite envenoming. However, existing elapid antivenoms are known for their low potency in neutralizing the neurotoxic activity of a-NTXs,...

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Main Authors: Chan, Yi Wei, Tan, Choo Hock, Heh, Choon Han, Tan, Kae Yi
Format: Article
Published: Frontiers Media 2023
Subjects:
RS Pharmacy and materia medica
Online Access:http://eprints.um.edu.my/38297/
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spelling my.um.eprints.382972024-06-24T04:30:06Z http://eprints.um.edu.my/38297/ An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms Chan, Yi Wei Tan, Choo Hock Heh, Choon Han Tan, Kae Yi RS Pharmacy and materia medica Introduction: Most elapid snakes produce venoms that contain alpha-neurotoxins (a-NTXs), which are proteins that cause post-synaptic blockade and paralysis in snakebite envenoming. However, existing elapid antivenoms are known for their low potency in neutralizing the neurotoxic activity of a-NTXs, while the immunological basis has not been elucidated.Methods: In this study, a structure-based major histocompatibility complex II (MHCII) epitope predictor of horse (Equus caballus), complemented with DM-editing determinant screening algorithm was adopted to assess the immunogenicity of a-NTXs in the venoms of major Asiatic elapids (Naja kaouthia, Ophiophagus hannah, Laticauda colubrina, Hydrophis schistosus, Hydrophis curtus).Results: The scoring metric M2R, representing the relative immunogenic performance of respective a-NTXs, showed all a-NTXs have an overall low M2R of <0.3, and most of the predicted binders feature non-optimal P1 anchor residues. The M2R scores correlate strongly (R-2 = 0.82) with the potency scores (p-score) generated based on the relative abundances of a-NTXs and the neutralization potency of commercial antivenoms.Discussion: The immunoinformatic analysis indicates that the inferior antigenicity of a-NTXs is not only due to their small molecular size but also the subpar immunogenicity affected by their amino acid composition. Structural modification with conjugation and synthetic epitope as immunogen may potentially enhance the immunogenicity for improved antivenom potency against a-NTXs of elapid snakes. Frontiers Media 2023-04 Article PeerReviewed Chan, Yi Wei and Tan, Choo Hock and Heh, Choon Han and Tan, Kae Yi (2023) An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms. Frontiers in Pharmacology, 14. ISSN 1663-9812, DOI https://doi.org/10.3389/fphar.2023.1143437 <https://doi.org/10.3389/fphar.2023.1143437>. 10.3389/fphar.2023.1143437
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic RS Pharmacy and materia medica
spellingShingle RS Pharmacy and materia medica
Chan, Yi Wei
Tan, Choo Hock
Heh, Choon Han
Tan, Kae Yi
An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms
description Introduction: Most elapid snakes produce venoms that contain alpha-neurotoxins (a-NTXs), which are proteins that cause post-synaptic blockade and paralysis in snakebite envenoming. However, existing elapid antivenoms are known for their low potency in neutralizing the neurotoxic activity of a-NTXs, while the immunological basis has not been elucidated.Methods: In this study, a structure-based major histocompatibility complex II (MHCII) epitope predictor of horse (Equus caballus), complemented with DM-editing determinant screening algorithm was adopted to assess the immunogenicity of a-NTXs in the venoms of major Asiatic elapids (Naja kaouthia, Ophiophagus hannah, Laticauda colubrina, Hydrophis schistosus, Hydrophis curtus).Results: The scoring metric M2R, representing the relative immunogenic performance of respective a-NTXs, showed all a-NTXs have an overall low M2R of <0.3, and most of the predicted binders feature non-optimal P1 anchor residues. The M2R scores correlate strongly (R-2 = 0.82) with the potency scores (p-score) generated based on the relative abundances of a-NTXs and the neutralization potency of commercial antivenoms.Discussion: The immunoinformatic analysis indicates that the inferior antigenicity of a-NTXs is not only due to their small molecular size but also the subpar immunogenicity affected by their amino acid composition. Structural modification with conjugation and synthetic epitope as immunogen may potentially enhance the immunogenicity for improved antivenom potency against a-NTXs of elapid snakes.
format Article
author Chan, Yi Wei
Tan, Choo Hock
Heh, Choon Han
Tan, Kae Yi
author_facet Chan, Yi Wei
Tan, Choo Hock
Heh, Choon Han
Tan, Kae Yi
author_sort Chan, Yi Wei
title An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms
title_short An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms
title_full An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms
title_fullStr An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms
title_full_unstemmed An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms
title_sort immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms
publisher Frontiers Media
publishDate 2023
url http://eprints.um.edu.my/38297/
_version_ 1805881103812132864
score 13.211869

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