Mutations in Main Protease of SARS CoV-2 Decreased Boceprevir Affinity
Yükleniyor...
Dosyalar
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
INST TECNOLOGIA PARANA
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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.
Açıklama
Anahtar Kelimeler
Boceprevir Affinity, Drug Validity, Main Protease, Mutation, SARS-CoV-2
Kaynak
Brazilian Archives of Biology and Technology
WoS Q Değeri
Q4
Scopus Q Değeri
Q2
Cilt
64
Sayı
e21200803
Künye
Akbulut, E. (2022). Mutations in Main Protease of SARS CoV-2 Decreased Boceprevir Affinity. Brazilian Archives of Biology and Technology, 64.
