A novel peptide analogue of spike glycoprotein shows antiviral properties against SARS-CoV-2: An in silico approach through molecular docking, molecular dynamics simulation and MM-PB/GBSA calculations (preprint)

At the very beginning of the new decade, the COVID-19 pandemic has badly hit modern human societies. SARS-CoV-2, the causative agent of COVID-19 carries dozens of new mutations in its genome. Herein, we made an effort to find new antiviral peptides (AVPs) against SARS-CoV-2. Gladly, with the help of Machine Learning algorithms, and Supported Vector Machine, we have invented three new AVPs against the SARS-CoV-2. Antiviral peptides viz., Seq12, Seq12m, and Seq13m can block the receptor binding domain (RBD) of the SARS-CoV-2, necessary for communication with the angiotensin-converting enzyme 2 (ACE2). In addition, these AVPs retain their antiviral properties, even after the insertion of dozens of new mutations (Rosetta, and FoldX based) in the RBD. Further, Seq12, and Seq12m showed negligible cytotoxicity. Besides, the binding free energy calculated using MM-PB/GBSA method is also in agreement with the molecular docking studies performed using HADDOCK. Furthermore, the molecular interactions between AVPs and the viral membrane protein (M) also showed a thermodynamically favorable interaction, suggesting it could eventually inhibit the viral re-packaging process. In conclusion, this study suggests AVPs viz., Seq12, Seq12m, and Seq13m embrace importance as a potential anti-SARS-CoV-2 therapeutic. These AVPs could also aid virus diagnostic tools in the future.

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2) (preprint)

Recent emergence of novel coronavirus (SARS-CoV-2) all over the world has resulted more than 33,106 global deaths. To date well-established therapeutics modules for infected patients are unknown. In this present initiative, molecular interactions between FDA-approved 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 RdRpHCV can efficiently bind to RdRp SARS-CoV-2 (ΔGAutoDock = -9.95 kcal mol-1) with an inhibition constant of 51.03 nM. Both the ΔGLondon and ΔGGBVI / WSA values were - 9.06 and - 6.67 kcal mol-1, respectively for binding of beclabuvir to RdRpSARS-CoV-2. In addition, beclabuvir has also shown better binding free energy with RdRpSARS-CoV-2 (ΔGvina = -8.0 kcal mol-1) than that observed with the Thumb 1 domain of RdRpHCV (ΔGvina = -7.1 kcal mol-1). InterProScan has suggested the RNA-directed 5'-3' polymerase activity exists within 549th to 776th amino acid residues of RdRpSARS-CoV, where the major amino acid residues interacting being 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 RdRpSARS-CoV-2, the enzyme essential for viral RNA synthesis. In conclusion, results suggest beclabuvir may serve as an anti-SARS-CoV-2 drug.

Anti-COVID-19 Effects of Ten Structurally Different Hydrolysable Tannins through Binding with the Catalytic-Closed Sites of COVID-19 Main Protease: An In-Silico Approach (preprint)

Coronavirus disease 2019 (COVID-19) was recently appeared 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.