Coronavirus epidemic 2019 (COVID-19), instigated by SARS-CoV-2 virus, is recently raising worldwide and inspiring global health worries. The main 3-chymotrypsin-like cysteine protease (3CL Pro) enzyme of SARS-CoV-2, which operates its replication, could be used as a medication discovery point. We therefore theoretically studied and docked the effects of 19 hydrolysable tannins on SARS-CoV-2 by assembling with the catalytic dyad residues of its 3CL pro using molecular operating environment (MOE 09). Results discovered that pedunculagin, tercatain, and castalin intensely interacted with the receptor binding site and catalytic dyad (Cys145 and His41) of SARS-CoV-2. Our analyses estimated that the top three hits might serve as potential inhibitor of SARS-CoV-2 leading molecules for additional optimization and drug development process to combat COVID-19. This study unleashed that tannins with specific structure could be utilized as natural inhibitors against COVID-19. Practical applications The 3CL Pro controls SARS-CoV-2 copying and manages its life series, which was targeted in case of SARS-CoV and MERS-CoV coronavirus. About 19 hydrolysable tannins were computed against 3CL pro of SARS-CoV-2. Pedunculagin, tercatain, and castalin interacted with Cys145 and His41 of SARS-CoV-2-3CL pro. Pedunculagin-SARS-CoV-2-3CL pro remain stable, with no obvious fluctuations. We predicted that the understandings gained in the current research may evidence valued for discovering and unindustrialized innovative natural inhibitors for COVID-19 in the nearby future.

Coronavirus disease 2019 (COVID-19) was recently raised and starting from China to all over the world. The viral main protease (3-chymotrypsin-like cysteine enzyme) controls COVID-19 duplication and manages its life cycle, making it a drug discovery target. Therefore, herein, we analyzed the theoretical approaches of 10 structurally different hydrolysable tannins as natural anti-COVID-19 through binding with the main protease of 2019-nCoV using molecular docking modelling via Molecular Operating Environment (MOE v2009) software. Our results revealed that there are top three hits may serve as potential anti-COVID-19 lead molecules for further optimization and drug development to control COVID-19. Pedunculagin, tercatain, and punicalin were found to faithfully interact with the receptor binding site and catalytic dyad (Cys145 and His41) of COVID-19 main protease, showing their successfully inhibit the protease enzyme of 2019-nCoV. We anticipated that this study would pave way for tannins based novel small molecules as more efficacious and selective anti-COVID-19 therapeutic compounds.

Graphical AbstractRedesigned enzyme for bioremediation.

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Recent emergence of novel coronavirus (SARS-CoV-2) in Wuhan, China has resulted more than 14,510 global deaths. To date well-established therapeutics modules for infected patients are unknown. In this present initiative, molecular interactions between well-known antiviral drugs against the Hepatitis-C virus (HCV) have been investigated theoretically against the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. HCV and SARS-CoV-2 are both +ssRNA viruses. At 25o C beclabuvir, a non-nucleoside inhibitor of the RdRp of the HCV can efficiently bind to RdRp of the SARS-CoV-2 (ΔGAutoDock = -9.95 kcal mol-1) with an inhibition constant of only 51.03 nM. Both the ΔGLondon and ΔGGBVI / WSA values were - 9.06 and - 6.67 kcal mol-1, respectively for SARS-CoV-2. In addition, beclabuvir also shows better binding free energy (ΔGvina = 9.7 kcal mol-1) than that of the Thumb 1 domain of RdRp of HCV (ΔGvina = 7.7 kcal mol-1). InterProScan has suggested the RNA-directed 5'-3' polymerase activity existed within 549 to 776 amino acid residues of RdRp. Moreover, major interacting amino acid residues were I591, Y621, C624, D625, A690, N693, L760, D762, D763 and E813-N817. Molecular interaction suggests occupancy of beclabuvir inside the active site environment of the RdRp which is essential for viral RNA synthesis. In conclusion, results suggest beclabuvir has high therapeutic potential as an anti-SARS-CoV-2 drug.