{"title":"Molecular Ion Channel Blockers of Influenza A and SARS-CoV-2 Viruses","authors":"Yu. N. Vorobjev","doi":"10.1134/s0026893324700353","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Molecules were proposed to block the functional cycles of the influenza virus A and SARS-CoV-2. The blocker molecules efficiently bind inside the M2 and E channels of influenza A and SARS-CoV-2 viruses and block diffusion of H<sup>+</sup>/K<sup>+</sup> ions, thus distorting the virus functional cycle. A family of positively charged (+2 e.u.) molecular blockers of H<sup>+</sup>/K<sup>+</sup> ion diffusion through the M2 and E channels was proposed. The blocker molecules were diazabicyclooctane (DABCO) derivatives and were investigated for affinity for the M2 and E channels. Thermal dynamics of native and mutant channel structures and blocker binding were modeled by exhaustive docking. Binding energy calculations revealed within-channel, blocking, and extra-channel binding sites in the M2 and E channel proteins. Blocker molecules with higher affinity for the blocking sites were proposed. The most probable amino acid mutations the M2 and E channels were considered, the efficiency of channel blocking was analyzed, and optimal structures were assumed for the blocker molecules.</p>","PeriodicalId":18734,"journal":{"name":"Molecular Biology","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1134/s0026893324700353","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Molecules were proposed to block the functional cycles of the influenza virus A and SARS-CoV-2. The blocker molecules efficiently bind inside the M2 and E channels of influenza A and SARS-CoV-2 viruses and block diffusion of H+/K+ ions, thus distorting the virus functional cycle. A family of positively charged (+2 e.u.) molecular blockers of H+/K+ ion diffusion through the M2 and E channels was proposed. The blocker molecules were diazabicyclooctane (DABCO) derivatives and were investigated for affinity for the M2 and E channels. Thermal dynamics of native and mutant channel structures and blocker binding were modeled by exhaustive docking. Binding energy calculations revealed within-channel, blocking, and extra-channel binding sites in the M2 and E channel proteins. Blocker molecules with higher affinity for the blocking sites were proposed. The most probable amino acid mutations the M2 and E channels were considered, the efficiency of channel blocking was analyzed, and optimal structures were assumed for the blocker molecules.
期刊介绍：
Molecular Biology is an international peer reviewed journal that covers a wide scope of problems in molecular, cell and computational biology including genomics, proteomics, bioinformatics, molecular virology and immunology, molecular development biology, molecular evolution and related areals. Molecular Biology publishes reviews, experimental and theoretical works. Every year, the journal publishes special issues devoted to most rapidly developing branches of physical-chemical biology and to the most outstanding scientists.
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