{"title":"利用基于分子指纹的筛选方法,探索 Mpox 病毒细胞表面结合蛋白潜在抑制剂的化学空间。","authors":"Dwaipayan Chaudhuri, Satyabrata Majumder, Joyeeta Datta, Kalyan Giri","doi":"10.1080/07391102.2023.2238087","DOIUrl":null,"url":null,"abstract":"<p><p>Mpox virus is the latest member of the Poxviridae family of which small pox virus is a member. Monekypox virus has led to thousands of infections across the globe. Poxvirus gains entry into the cell making use of glycosaminoglycans like chondroitin sulphate and heparan sulphate. The interaction of the Mpox virus protein E8L also called cell surface binding protein is crucial for host cell attachment, membrane fusion and viral entry into the host cell leading to establishment of infection thus making this protein a very attractive therapeutic target. In this study we have tried to utilize the chondroitin sulphate binding groove present in the protein and identify molecules which are structurally similar to chondroitin sulphate. These molecules can thus occupy the same pocket but with a better binding affinity than chondroitin sulphate in order to outcompete the latter molecule from binding to the E8L protein and thus prevent it from performing its function. This study may pave the way for development of highly efficient therapeutics against the Mpox virus and further curb its infective potential.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring the chemical space for potential inhibitors against cell surface binding protein of Mpox virus using molecular fingerprint based screening approach.\",\"authors\":\"Dwaipayan Chaudhuri, Satyabrata Majumder, Joyeeta Datta, Kalyan Giri\",\"doi\":\"10.1080/07391102.2023.2238087\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Mpox virus is the latest member of the Poxviridae family of which small pox virus is a member. Monekypox virus has led to thousands of infections across the globe. Poxvirus gains entry into the cell making use of glycosaminoglycans like chondroitin sulphate and heparan sulphate. The interaction of the Mpox virus protein E8L also called cell surface binding protein is crucial for host cell attachment, membrane fusion and viral entry into the host cell leading to establishment of infection thus making this protein a very attractive therapeutic target. In this study we have tried to utilize the chondroitin sulphate binding groove present in the protein and identify molecules which are structurally similar to chondroitin sulphate. These molecules can thus occupy the same pocket but with a better binding affinity than chondroitin sulphate in order to outcompete the latter molecule from binding to the E8L protein and thus prevent it from performing its function. This study may pave the way for development of highly efficient therapeutics against the Mpox virus and further curb its infective potential.Communicated by Ramaswamy H. Sarma.</p>\",\"PeriodicalId\":15272,\"journal\":{\"name\":\"Journal of Biomolecular Structure & Dynamics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biomolecular Structure & Dynamics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/07391102.2023.2238087\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/7/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biomolecular Structure & Dynamics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/07391102.2023.2238087","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/7/22 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Exploring the chemical space for potential inhibitors against cell surface binding protein of Mpox virus using molecular fingerprint based screening approach.
Mpox virus is the latest member of the Poxviridae family of which small pox virus is a member. Monekypox virus has led to thousands of infections across the globe. Poxvirus gains entry into the cell making use of glycosaminoglycans like chondroitin sulphate and heparan sulphate. The interaction of the Mpox virus protein E8L also called cell surface binding protein is crucial for host cell attachment, membrane fusion and viral entry into the host cell leading to establishment of infection thus making this protein a very attractive therapeutic target. In this study we have tried to utilize the chondroitin sulphate binding groove present in the protein and identify molecules which are structurally similar to chondroitin sulphate. These molecules can thus occupy the same pocket but with a better binding affinity than chondroitin sulphate in order to outcompete the latter molecule from binding to the E8L protein and thus prevent it from performing its function. This study may pave the way for development of highly efficient therapeutics against the Mpox virus and further curb its infective potential.Communicated by Ramaswamy H. Sarma.
期刊介绍:
The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.