Abstract:
Objective To predict high-risk amino acid mutations in mpox virus and provide important targets for the development of vaccines and therapeutic drugs.
Methods The study focused on key antigen proteins of the mpox virus: A27L, A29L, B5R, H3L, L1R, M1R and C9L. The immune escape ability of all possible amino acid mutations in these antigen proteins was predicted and scored using three indicators: fitness, variability, and accessibility. The top 10.00% of amino acid mutation foci for each antigen protein, based on these scores, were selected for pathogenicity and structural damage analysis.
Results A total of 4 902 amino acid mutation foci with high immune escape ability were identified, most of which were potential high-risk mutations. The foci with high immune escape ability were mainly located on antigen epitopes. In the selected foci, 17.14% exhibited high pathogenicity, with protein structural damage mainly resulting from disruptions in protein structure and interactions. Finally, 32 high-risk amino acid mutation foci with high immune escape ability, pathogenicity, and structural damage were identified.
Conclusion The prediction of 32 high-risk amino acid mutations in mpox virus antigen protein, provided key targets for the development of mpox virus vaccines and therapeutic drugs as well as guidance for the implementation of control measures.
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