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

Abstract

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.

In Silico Exploration of Bisphosphonate Scaffolds as Potential Inhibitors of SARS-CoV-2 RdRp for COVID-19 and PASC

“…The number of drugs that passed the filter was 1,398. To further reduce this number, a filter corresponding to the number of rotatable bonds was applied, as the drugs having fewer rotatable bonds are acceptable [63,76]. With this filter, 628 molecules were obtained, which were further subjected to molecular docking using the extra precision (XP) mode.…”

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

“…For example, signs and symptoms [38], mode of transmission [39], WHO-solidarity trials [40], contact tracing by mobiles apps such as "Arogya Setu" by India [41], CRISPR-Cas based rapid diagnostic of SARS-CoV-2 [42], and also monitoring daily cases by crowd-sourcing from https://www.covid19india.org/. Moreover, several reports are coming out as preprints and formal peer-review publications about repurposing known drugs [2] and antiviral drugs against the SARS-CoV-2 [43]. Reports suggesting possible anti-COVID-19 effects of different phytochemicals by in silico screening methods [4].…”

“…At present, the entire world is facing challenges in handing the COVID-19 pandemic [1]. Reports are coming out from different countries which suggest repurposing known antiviral drugs against COVID-19 could be fruitful [2][3][4]. However, none of them have reached a nal de nitive treatment for COVID-19.…”

Comparative Study of Drug Likeness and Pharmacokinetic Properties of Synthetic Antiviral Drugs to that of Remdesivir: In-silico Approach

“…The positive single-stranded RNA genome of CoVs encodes the 2 significant genes, i.e., OPF1a and ORF1b, which encodes 16nsp (non-structural protein). ORF1a encodes form nsp1-nsp11 and ORF1b encode for nsp12-nsp16 [14,15].…”