Investigation of changes in protein stability and substrate affinity of 3CL-protease of SARS-CoV-2 caused by mutations

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dc.authorid0000-0002-7526-9835en_US
dc.contributor.authorAkbulut, Ekrem
dc.date.accessioned2022-07-01T06:37:56Z
dc.date.available2022-07-01T06:37:56Z
dc.date.issued2022en_US
dc.departmentMTÖ Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümüen_US
dc.descriptionEkrem Akbulut, Malatya Turgut Ozal University, Faculty of Engineering and Natural Sciences, Department of Bioengineering, Malatya, Turkey.en_US
dc.descriptionGenetics and Molecular Biology, 45, 2, e20210404 (2022) Copyright © Sociedade Brasileira de Genética. DOI: https://doi.org/10.1590/1678-4685-GMB-2021-0404en_US
dc.description.abstract3CLpro of SARS-CoV-2 is one of the enzymes required for the replication process of the virus responsible for the COVID-19 pandemic. In this study, changes in protein stability and substrate affinity caused by mutations were investigated to stir the development of potent inhibitors. Sequence data of samples were obtained from the NCBI Virus database. Mutation analyses were performed with RDP4 and MegaX. 3CLpro tertiary models were created using Robetta. Molecular docking for peptidomimetic substrate and inhibitor ligand was done with Autodock v4.2 and Haddock v2.4. Protein stability analysis was performed using mCSM stability and DynaMut2. Twenty-four missense mutations in 3CLpro were identified in this study. Changes in the 3CLpro structure induced by the mutations Met49Thr, Leu167Ser, and Val202Ala resulted in significant levels of instability (-2.029,-2.612,-2.177 kcal.mol-1, respectively). The lowest interaction energy for substrate was-58.7 kcal.mol-1 and-62.6 kcal.mol-1 in wild-type and mutant, respectively. The lowest docking energy for ligand was-6.19 and-9.52 kcal.mol-1 for wild-type and mutant, respectively. This study reports for the first time that mutations cause increased substrate affinity of 3CLpro from SARS-CoV-2. This research provides important data for the development of potent peptidomimetic inhibitors for the treatment of COVID-19.en_US
dc.identifier.citationAkbulut, E. (2022). Investigation of changes in protein stability and substrate affinity of 3CL-protease of SARS-CoV-2 caused by mutations. Genetics and Molecular Biology, 45(2).en_US
dc.identifier.doi10.1590/1678-4685-GMB-2021-0404
dc.identifier.endpage11en_US
dc.identifier.issn1415-4757en_US
dc.identifier.issn1678-4685en_US
dc.identifier.issue2en_US
dc.identifier.scopus2-s2.0-85131018603en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage1en_US
dc.identifier.urihttps://doi.org/10.1590/1678-4685-GMB-2021-0404
dc.identifier.urihttps://hdl.handle.net/20.500.12899/1147
dc.identifier.volume45en_US
dc.identifier.wosWOS:000792328300001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.institutionauthorAkbulut, Ekrem
dc.language.isoenen_US
dc.publisherSociedade Brasileira de Geneticaen_US
dc.relation.ispartofGenetics and Molecular Biologyen_US
dc.relation.publicationcategoryMakale - Ulusal Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject3CL-proteaseen_US
dc.subjectMutation analysisen_US
dc.subjectProtein stabilityen_US
dc.subjectSARS-CoV-2 genomeen_US
dc.subjectSubstrate affinityen_US
dc.titleInvestigation of changes in protein stability and substrate affinity of 3CL-protease of SARS-CoV-2 caused by mutationsen_US
dc.typeArticleen_US

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