{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Jana ID"],"funding":["BLRD VA","NCI NIH HHS"],"pubmed_abstract":["As newer variants of SARS-CoV-2 continue to pose major threats to global human health and economy, identifying novel druggable antiviral targets is the key towards sustenance. Here, we identify an evolutionary conserved E-L-L motif present within the HR2 domain of all human and non-human coronavirus spike (S) proteins that play a crucial role in stabilizing the post-fusion six-helix bundle (6-HB) structure and thus, fusion-mediated viral entry. Mutations within this motif reduce the fusogenicity of the S protein without affecting its stability or membrane localization. We found that posaconazole, an FDA-approved drug, binds to this E-L-L motif resulting in effective inhibition of SARS-CoV-2 infection in cells. While posaconazole exhibits high efficacy towards blocking S protein-mediated vi"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2022.03.16.484554"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8936095"],"repository":["biostudies-literature"],"pubmed_title":["Targeting an evolutionarily conserved \"E-L-L\" motif in the spike protein to develop a small molecule fusion inhibitor against SARS-CoV-2."],"pmcid":["PMC8936095"],"funding_grant_id":["IK6 BX004212","I01 BX005490","IK6 BX003778","R01 CA180758"],"pubmed_authors":["Banerjee S","Ghosh A","Das AK","Bhattacharya P","Das S","Mohapatra SS","Aditya S","Srikrishnan S","Roy A","McGill AR","Chandran B","Mohapatra S","Mondal A","Mayilsamy K","Bhattacharje G","Jana ID","Basak A","Bhimsaria D"],"additional_accession":[]},"is_claimable":false,"name":"Targeting an evolutionarily conserved \"E-L-L\" motif in the spike protein to develop a small molecule fusion inhibitor against SARS-CoV-2.","description":"As newer variants of SARS-CoV-2 continue to pose major threats to global human health and economy, identifying novel druggable antiviral targets is the key towards sustenance. Here, we identify an evolutionary conserved E-L-L motif present within the HR2 domain of all human and non-human coronavirus spike (S) proteins that play a crucial role in stabilizing the post-fusion six-helix bundle (6-HB) structure and thus, fusion-mediated viral entry. Mutations within this motif reduce the fusogenicity of the S protein without affecting its stability or membrane localization. We found that posaconazole, an FDA-approved drug, binds to this E-L-L motif resulting in effective inhibition of SARS-CoV-2 infection in cells. While posaconazole exhibits high efficacy towards blocking S protein-mediated vi","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-04-08T17:31:46.134Z","creation":"2024-11-21T02:17:34.112Z"},"accession":"S-EPMC8936095","cross_references":{"pubmed":["35313575"],"doi":["10.1101/2022.03.16.484554"]}}