Mutations in Main Protease of SARS CoV-2 Decreased Boceprevir Affinity
| dc.authorid | 0000-0002-7526-9835 | en_US |
| dc.date.accessioned | 2022-03-18T10:30:35Z | |
| dc.date.available | 2022-03-18T10:30:35Z | |
| dc.date.issued | 2022 | en_US |
| dc.department | MTÖ Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü | en_US |
| dc.description.abstract | The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health emergency. The main protease (Mpro) is crucial for the life cycle of coronaviruses. Boceprevir is a potential inhibitor and drug candidate for the Mpro of SARS-CoV-2. In this study, changes in the protein structure of the Mpro due to mutations in SARS-CoV-2 and the effects of these changes on boceprevir affinity, an important potential therapeutic agent, were investigated. The mutations were analyzed with RDP4 and MegaX. A three-dimensional model of mutant Mpro was generated by ProMod3. Qualitative Model Energy Analysis, ProSA, and MolProbity tools were used for structural validation and modeling of the wild-type and mutant Mpro proteins. Topological differences of the wild-type and mutant Mpro were calculated with the i-Tasser TM-Score. Molecular docking was performed using AutoDock 4.2. Functional dynamic structure models were created with DynOmics. Seven mutations (L89F, K90R, P108S, A191V, T224A, A234V and S254F) were detected in the Mpro of SARS-CoV-2. The mutations caused a decrease in the affinity of boceprevir, a potential protease inhibitor. The boceprevir was docked to the active site of Mpro, and the binding energies were ?10.34 and ?9.41 kcal.mol-1 for the wild-type and the mutant, respectively. The Debye–Waller factors calculated by elastic network model analysis were 0.58 and 0.64 Å2 for the wild-type Mpro and mutant Mpro, respectively. Mutations in structures that are important drug targets for SARS-CoV-2 may render existing therapeutics ineffective in its treatment. | en_US |
| dc.identifier.citation | Akbulut, E. (2022). Mutations in Main Protease of SARS CoV-2 Decreased Boceprevir Affinity. Brazilian Archives of Biology and Technology, 64. | en_US |
| dc.identifier.doi | 10.1590/1678-4324-2021200803 | |
| dc.identifier.issn | 1516-8913 | en_US |
| dc.identifier.issn | 1678-4324 | en_US |
| dc.identifier.issue | e21200803 | en_US |
| dc.identifier.scopus | 2-s2.0-85125948750 | en_US |
| dc.identifier.scopusquality | Q2 | en_US |
| dc.identifier.uri | https://doi.org/10.1590/1678-4324-2021200803 | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12899/696 | |
| dc.identifier.volume | 64 | en_US |
| dc.identifier.wos | WOS:000760428500001 | en_US |
| dc.identifier.wosquality | Q4 | en_US |
| dc.indekslendigikaynak | Scopus | en_US |
| dc.indekslendigikaynak | PubMed | en_US |
| dc.institutionauthor | Akbulut, Ekrem | |
| dc.language.iso | en | en_US |
| dc.publisher | INST TECNOLOGIA PARANA | en_US |
| dc.relation.ispartof | Brazilian Archives of Biology and Technology | en_US |
| dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
| dc.rights | info:eu-repo/semantics/closedAccess | en_US |
| dc.subject | Boceprevir Affinity | en_US |
| dc.subject | Drug Validity | en_US |
| dc.subject | Main Protease | en_US |
| dc.subject | Mutation | en_US |
| dc.subject | SARS-CoV-2 | en_US |
| dc.title | Mutations in Main Protease of SARS CoV-2 Decreased Boceprevir Affinity | en_US |
| dc.title.alternative | Boceprevir is a potential therapeutic that targets the main protease of SARS-CoV-2 | en_US |
| dc.title.alternative | Mutations change the inhibitory binding pattern in the catalytic domain of the main protease | en_US |
| dc.title.alternative | Mutations of main protease of SARS-CoV-2 cause a decrease in boceprevir affinity | en_US |
| dc.type | Article | en_US |
