Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)
Year: 2020
Type: preprint
Abstract: 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.
Source: Preprints.org
Institutions: Vidyasagar University, China Medical University, University of Würzburg, Universitätsklinikum Würzburg, China Medical University Hospital, Nizhniy Novgorod Research Institute of Epidemiology and Microbiology named after Academician I.N. Blokhina, N. I. Lobachevsky State University of Nizhny Novgorod, Huazhong Agricultural University, Benha University, Jinan University
Language: English
Subfield: Drug Discovery
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4232909948