Version 1
: Received: 25 March 2020 / Approved: 26 March 2020 / Online: 26 March 2020 (15:18:38 CET)
Version 2
: Received: 31 March 2020 / Approved: 2 April 2020 / Online: 2 April 2020 (11:25:57 CEST)
How to cite:
Dutta, K.; Shityakov, S.; Morozova, O.; Khalifa, I.; Zhang, J.; Zhu, W.; Panda, A.; Ghosh, C. Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2). Preprints2020, 2020030395. https://doi.org/10.20944/preprints202003.0395.v2.
Dutta, K.; Shityakov, S.; Morozova, O.; Khalifa, I.; Zhang, J.; Zhu, W.; Panda, A.; Ghosh, C. Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2). Preprints 2020, 2020030395. https://doi.org/10.20944/preprints202003.0395.v2.
Cite as:
Dutta, K.; Shityakov, S.; Morozova, O.; Khalifa, I.; Zhang, J.; Zhu, W.; Panda, A.; Ghosh, C. Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2). Preprints2020, 2020030395. https://doi.org/10.20944/preprints202003.0395.v2.
Dutta, K.; Shityakov, S.; Morozova, O.; Khalifa, I.; Zhang, J.; Zhu, W.; Panda, A.; Ghosh, C. Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2). Preprints 2020, 2020030395. https://doi.org/10.20944/preprints202003.0395.v2.
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.
Keywords
Novel coronavirus (SARS-CoV-2); RdRp; HCV; beclabuvir; in silico; molecular docking
Subject
LIFE SCIENCES, Biotechnology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Commenter: Kunal Dutta
Commenter's Conflict of Interests: Author