Key result
Beclabuvir efficiently binds to the RNA-dependent RNA polymerase of SARS-CoV-2 in silico, demonstrating a binding free energy of -9.95 kcal/mol and an inhibition constant of 51.03 nM.
Why the study?
SARS-CoV-2 emerged causing widespread deaths, but well-established therapeutic modules for infected patients were unknown.
Computational modeling suggests beclabuvir has high theoretical binding affinity to the SARS-CoV-2 RNA-dependent RNA polymerase, indicating potential as an antiviral.
Answers are grounded in this paper and cite their sources.
Theoretical interactions of HCV antivirals with SARS-CoV-2 RdRp may warrant lab validation; leaves open any clinical role in COVID-19.
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.
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Dutta et al. (2020) studied SARS-CoV-2. Beclabuvir was evaluated on Molecular interaction and binding free energy with RdRp of SARS-CoV-2. Beclabuvir efficiently binds to the RNA-dependent RNA polymerase of SARS-CoV-2 in silico, demonstrating a binding free energy of -9.95 kcal/mol and an inhibition constant of 51.03 nM.
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