Binary-QSAR guided virtual screening of FDA approved drugs and compounds in clinical investigation against SARS-CoV-2 main protease

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dc.contributor.authorOktay, Lalehan
dc.contributor.authorErdemoglu, Ece
dc.contributor.authorTolu, Ilayda
dc.contributor.authorYumak, Yesim
dc.contributor.authorOzcan, Aysenur
dc.contributor.authorAcar, Elif
dc.contributor.authorBuyukkilic, Sehriban
dc.date.accessioned2024-02-23T14:35:28Z
dc.date.available2024-02-23T14:35:28Z
dc.date.issued2021
dc.departmentNEÜen_US
dc.description.abstractWith the emergence of the new SARS-CoV-2 virus, drug repurposing studies have gained substantial importance. Combined with the efficacy of recent improvements in ligand- and target-based virtual screening approaches, virtual screening has become faster and more productive than ever. In the current study, an FDA library of approved drugs and compounds under clinical investigation were screened for their antiviral activity using the antiviral therapeutic activity binary QSAR model of the MetaCore/MetaDrug platform. Among 6733-compound collection, we found 370 compounds with a normalized therapeutic activity value greater than a cutoff of 0.75. Only these selected compounds were used for molecular docking studies against the SARS-CoV-2 main protease (Mpro). After initial short (10 ns) molecular dynamics (MD) simulations with the top-50 docking scored compounds and following molecular mechanics generalized born surface area (MM/GBSA) calculations, top-10 compounds were subjected to longer (100 ns) MD simulations and end-point MM/GBSA estimations. Our virtual screening protocol yielded Cefuroxime pivoxetil, an ester prodrug of second-generation cephalosporin antibiotic Cefuroxime, as being a considerable molecule for drug repurposing against the SARS-CoV-2 M-pro.en_US
dc.description.sponsorshipTUBITAK 2247-C STAR program; Scientific Research Projects Commission of Bahcesehir University [BAU.BAP.2020.01]en_US
dc.description.sponsorshipThis study was supported by the TUBITAK 2247-C STAR program. This study was also funded by Scientific Research Projects Commission of Bahcesehir University. Project number: BAU.BAP.2020.01.en_US
dc.identifier.doi10.3906/biy-2106-61
dc.identifier.endpage+en_US
dc.identifier.issn1300-0152
dc.identifier.issn1303-6092
dc.identifier.issue4en_US
dc.identifier.pmid34803447en_US
dc.identifier.scopus2-s2.0-85114263105en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage459en_US
dc.identifier.urihttps://doi.org/10.3906/biy-2106-61
dc.identifier.urihttps://hdl.handle.net/20.500.12452/16039
dc.identifier.volume45en_US
dc.identifier.wosWOS:000691376800009en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTubitak Scientific & Technological Research Council Turkeyen_US
dc.relation.ispartofTurkish Journal Of Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectBinary Qsaren_US
dc.subjectVirtual Screeningen_US
dc.subjectDrug Repurposingen_US
dc.subjectSars-Cov-2en_US
dc.titleBinary-QSAR guided virtual screening of FDA approved drugs and compounds in clinical investigation against SARS-CoV-2 main proteaseen_US
dc.typeArticleen_US

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