Identification of High Affinity and Low Molecular Alternatives of Boceprevir Against SARS-CoV-2 Main Protease: A Virtual Screening Approach

Overview

Journal Chem Phys Lett

Date 2021 Feb 24

PMID 33623170

Citations 8

Authors

Subhomoi Borkotoky

Manidipa Banerjee

Gyan Prakash Modi

Vikash Kumar Dubey

Affiliations

Soon will be listed here.

Abstract

SARS-CoV-2 has posed global challenge for healthcare due to COVID-19. The main protease (M) of this virus is considered as a major target for drug development efforts. In this work, we have used virtual screening approach with molecular dynamics simulations to identify high affinity and low molecular weight alternatives of boceprevir, a repurposed drug currently being evaluated against M. Out of 180 compounds screened, two boceprevir analogs (PubChem ID: 57841991 and 58606278) were reported as potential alternatives with comparable predicted protease inhibitor potential and pharmacological properties. Further experimental validation of the reported compounds may contribute to the ongoing investigation of boceprevir.

Citing Articles

An Overview of SARS-CoV-2 Potential Targets, Inhibitors, and Computational Insights to Enrich the Promising Treatment Strategies.

Kumawat P, Agarwal L, Sharma K Curr Microbiol. 2024; 81(7):169.

PMID: 38733424 DOI: 10.1007/s00284-024-03671-3.

In silico study to identify novel NEK7 inhibitors from natural sources by a combination strategy.

Zhang H, Lu C, Yao Q, Jiao Q Mol Divers. 2024; 29(1):139-162.

PMID: 38598164 DOI: 10.1007/s11030-024-10838-4.

Repurposing the in-house generated Alzheimer's disease targeting molecules through computational and preliminary in-vitro studies for the management of SARS-coronavirus-2.

Singh G, Thomas J, Wadhawa S, Kashyap A, Rahaman S, Borkotoky S Mol Divers. 2023; 28(5):2847-2862.

PMID: 37749454 DOI: 10.1007/s11030-023-10717-4.

The Application of MD Simulation to Lead Identification, Vaccine Design, and Structural Studies in Combat against Leishmaniasis - A Review.

Vijayakumar S, Laxman Kumar L, Borkotoky S, Murali A Mini Rev Med Chem. 2023; 24(11):1089-1111.

PMID: 37680156 DOI: 10.2174/1389557523666230901105231.

An integrative reverse vaccinology, immunoinformatic, docking and simulation approaches towards designing of multi-epitopes based vaccine against monkeypox virus.

Ullah A, Shahid F, Ul Haq M, Tahir Ul Qamar M, Irfan M, Shaker B J Biomol Struct Dyn. 2022; 41(16):7821-7834.

PMID: 36129135 PMC: 9527787. DOI: 10.1080/07391102.2022.2125441.

References

Pettersen E, Goddard T, Huang C, Couch G, Greenblatt D, Meng E . UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004; 25(13):1605-12. DOI: 10.1002/jcc.20084. View

Schuttelkopf A, van Aalten D . PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr D Biol Crystallogr. 2004; 60(Pt 8):1355-63. DOI: 10.1107/S0907444904011679. View

Chen J, Wu S, Zhang Q, Yin Z, Zhang L . α-Glucosidase inhibitory effect of anthocyanins from Cinnamomum camphora fruit: Inhibition kinetics and mechanistic insights through in vitro and in silico studies. Int J Biol Macromol. 2019; 143:696-703. DOI: 10.1016/j.ijbiomac.2019.09.091. View

Verma S, Twilley D, Esmear T, Oosthuizen C, Reid A, Nel M . Anti-SARS-CoV Natural Products With the Potential to Inhibit SARS-CoV-2 (COVID-19). Front Pharmacol. 2020; 11:561334. PMC: 7546787. DOI: 10.3389/fphar.2020.561334. View

Rastogi M, Pandey N, Shukla A, Singh S . SARS coronavirus 2: from genome to infectome. Respir Res. 2020; 21(1):318. PMC: 7706175. DOI: 10.1186/s12931-020-01581-z. View

Zhang Z, Zhang Y, Li X, Zhang H, Xiao S, Deng F . A cell-based large-scale screening of natural compounds for inhibitors of SARS-CoV-2. Signal Transduct Target Ther. 2020; 5(1):218. PMC: 7532339. DOI: 10.1038/s41392-020-00343-z. View

Paasche A, Zipper A, Schafer S, Ziebuhr J, Schirmeister T, Engels B . Evidence for substrate binding-induced zwitterion formation in the catalytic Cys-His dyad of the SARS-CoV main protease. Biochemistry. 2014; 53(37):5930-46. DOI: 10.1021/bi400604t. View

Kim S, Thiessen P, Bolton E, Chen J, Fu G, Gindulyte A . PubChem Substance and Compound databases. Nucleic Acids Res. 2015; 44(D1):D1202-13. PMC: 4702940. DOI: 10.1093/nar/gkv951. View

Fu L, Ye F, Feng Y, Yu F, Wang Q, Wu Y . Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease. Nat Commun. 2020; 11(1):4417. PMC: 7474075. DOI: 10.1038/s41467-020-18233-x. View

10.

Schmid N, Eichenberger A, Choutko A, Riniker S, Winger M, Mark A . Definition and testing of the GROMOS force-field versions 54A7 and 54B7. Eur Biophys J. 2011; 40(7):843-56. DOI: 10.1007/s00249-011-0700-9. View

11.

Fiorucci D, Milletti E, Orofino F, Brizzi A, Mugnaini C, Corelli F . Computational drug repurposing for the identification of SARS-CoV-2 main protease inhibitors. J Biomol Struct Dyn. 2020; 39(16):6242-6248. PMC: 7441760. DOI: 10.1080/07391102.2020.1796805. View

12.

Ma R, Wong S, Ge L, Shaw C, Siu S, Kwok H . and MD Simulation Study to Explore Physicochemical Parameters for Antibacterial Peptide to Become Potent Anticancer Peptide. Mol Ther Oncolytics. 2020; 16:7-19. PMC: 6940675. DOI: 10.1016/j.omto.2019.12.001. View

13.

Ma C, Sacco M, Hurst B, Townsend J, Hu Y, Szeto T . Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Res. 2020; 30(8):678-692. PMC: 7294525. DOI: 10.1038/s41422-020-0356-z. View

14.

Zhao Y, Le J, Abraham M, Hersey A, Eddershaw P, Luscombe C . Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure-activity relationship (QSAR) with the Abraham descriptors. J Pharm Sci. 2001; 90(6):749-84. DOI: 10.1002/jps.1031. View

15.

Rehman M, Alajmi M, Hussain A . Natural Compounds as Inhibitors of SARS-CoV-2 Main Protease (3CLpro): A Molecular Docking and Simulation Approach to Combat COVID-19. Curr Pharm Des. 2020; 27(33):3577-3589. DOI: 10.2174/1381612826999201116195851. View

16.

Blanchard J, Elowe N, Huitema C, Fortin P, Cechetto J, Eltis L . High-throughput screening identifies inhibitors of the SARS coronavirus main proteinase. Chem Biol. 2004; 11(10):1445-53. PMC: 7134594. DOI: 10.1016/j.chembiol.2004.08.011. View

17.

Bacha U, Barrila J, Velazquez-Campoy A, Leavitt S, Freire E . Identification of novel inhibitors of the SARS coronavirus main protease 3CLpro. Biochemistry. 2004; 43(17):4906-12. DOI: 10.1021/bi0361766. View

18.

Kneller D, Phillips G, ONeill H, Jedrzejczak R, Stols L, Langan P . Structural plasticity of SARS-CoV-2 3CL M active site cavity revealed by room temperature X-ray crystallography. Nat Commun. 2020; 11(1):3202. PMC: 7314768. DOI: 10.1038/s41467-020-16954-7. View

19.

Li Z, Li X, Huang Y, Wu Y, Liu R, Zhou L . Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs. Proc Natl Acad Sci U S A. 2020; 117(44):27381-27387. PMC: 7959488. DOI: 10.1073/pnas.2010470117. View

20.

Rizza S, Talwani R, Nehra V, Temesgen Z . Boceprevir. Drugs Today (Barc). 2011; 47(10):743-51. DOI: 10.1358/dot.2011.47.10.1656503. View