The coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health emergency. The main protease (M pro ) is crucial for the life cycle of coronaviruses. Boceprevir is a potential inhibitor and drug candidate for the M pro of SARS-CoV-2. In this study, changes in the protein structure of the M pro due to mutations in SARS-CoV-2 and the effects of these changes on boceprevir affinity, an important potential therapeutic agent, were investigated.

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... he mutations were analyzed with RDP4 and MegaX. A three-dimensional model of mutant M pro 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 M pro proteins. Topological differences of the wild-type and mutant M pro 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 M pro 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 M pro , 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 Å 2 for the wild-type M pro and mutant M pro , respectively. Mutations in structures that are important drug targets for SARS-CoV-2 may render existing therapeutics ineffective in its treatment.