%0 Journal Article %1 Dutta_2020 %A Dutta, Kunal %A Shityakov, Sergey %A Morozova, Olga %A Khalifa, Ibrahim %A Zhang, Jin %A Panda, Amiya %A Ghosh, Chandradipa %D 2020 %I MDPI AG %K %R 10.20944/preprints202003.0395.v1 %T Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2) %U https://doi.org/10.20944%2Fpreprints202003.0395.v1 %X 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.

@article{Dutta_2020, 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.}, added-at = {2020-05-30T19:14:51.000+0200}, author = {Dutta, Kunal and Shityakov, Sergey and Morozova, Olga and Khalifa, Ibrahim and Zhang, Jin and Panda, Amiya and Ghosh, Chandradipa}, biburl = {https://www.bibsonomy.org/bibtex/2e30a22e193e53a4f73597f8aee4e1982/duttabio}, doi = {10.20944/preprints202003.0395.v1}, interhash = {fe1e82f2c2fe995d90b2d04b51a396a1}, intrahash = {e30a22e193e53a4f73597f8aee4e1982}, keywords = {}, month = mar, publisher = {{MDPI} {AG}}, timestamp = {2020-05-30T19:14:51.000+0200}, title = {Beclabuvir can Inhibit the {RNA}-dependent {RNA} Polymerase of Newly Emerged Novel Coronavirus ({SARS}-{CoV}-2)}, url = {https://doi.org/10.20944%2Fpreprints202003.0395.v1}, year = 2020 }