Computer-aided approaches reveal trihydroxychroman and pyrazolone derivatives as potential inhibitors of SARS-CoV-2 virus main protease

Atatreh, Noor; Hasan, Shaima; Ali, Bassam R.; Ghattas, Mohammad A.

doi:10.2478/acph-2021-0040

Abstract

COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). The aim of this study is to target the SARS-CoV-2 virus main protease (M^pro) via structure-based virtual screening. Consequently, > 580,000 ligands were processed via several filtration and docking steps, then the top 21 compounds were analysed extensively via MM-GBSA scoring and molecular dynamic simulations. Interestingly, the top compounds showed favorable binding energies and binding patterns to the protease enzyme, forming interactions with several key residues. Trihydroxychroman and pyrazolone derivatives, SN02 and SN18 ligands, exhibited very promising binding modes along with the best MM-GBSA scoring of –40.9 and –41.2 kcal mol⁻¹, resp. MD simulations of 300 ns for the ligand-protein complexes of SN02 and SN18 affirmed the previously attained results of the potential inhibition activity of these two ligands. These potential inhibitors can be the starting point for further studies to pave way for the discovery of new antiviral drugs for SARS-CoV-2.

References

1. R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. Wu, W. Wang, H. Song, B. Huang, N. Zhu, Y. Bi, X. Ma, F. Zhan, L Wang, T. Hu, H. Zhou, Z Hu, W. Zhou, L. Zhao, J. Chen, Y. Meng, J.Wang, Y. Lin, J. Yuan, Z. Xie, J. Ma, W. J. Liu, D. Wang, W. Xu, E. C. Holmes, G. F. Gao, G. Wu, W. Chen, W. Shi and W. Tan, Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding, Lancet395 (2020) 565–574; https://doi.org/10.1016/S0140-6736(20)30251-810.1016/S0140-6736(20)30251-8
Search in Google Scholar Back to article
2. M. Yuan, N. C. Wu, X. Zhu, C. D. Lee, R. T. Y. So, H. Lv, C. K. P. Mok and I. A. Wilson, A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV, Science368 (2020) 630–633; https://doi.org/10.1126%2Fscience.abb726910.1126/science.abb7269716439132245784
Search in Google Scholar Back to article
3. A. Wu, Y. Peng, B. Huang, X. Ding, X. Wang, P. Niu, J. Meng, Z. Zhu, Z. Zhang, J. Wang, J. Sheng, L. Quan, Z. Xia, W. Tan, G. Cheng and T. Jiang, Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China, Cell Host Microbe27 (2020) 325–328; https://doi.org/10.1016/j.chom.2020.02.00110.1016/j.chom.2020.02.001715451432035028
Search in Google Scholar Back to article
4. Z. Jin, X. Du, Y. Xu, Y. Deng, M. Liu, Y. Zhao, B. Zhang, X. Li, L. Zhang, C. Peng, Y. Duan, J. Yu, L. Wang, K. Yang, F. Liu, R. Jiang, X. Yang, T. You, X. Liu, X. Yang, F. Bai, H. Liu, X. Liu, L. W. Guddat, W. Xu, G. Xiao, C. Qin, Z. Shi, H. Jiang, Z. Rao and H. Yang, Structure of M(pro) from SARS-CoV-2 and discovery of its inhibitors, Nature582 (2020) 289–293; https://doi.org/10.1038/s41586-020-2223-y10.1038/s41586-020-2223-y32272481
Search in Google Scholar Back to article
5. A. Shulla, T. Heald-Sargent, G. Subramanya, J. Zhao, S. Perlman and T. Gallagher, A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry, J. Virol. 85 (2011) 873–882; https://doi.org/10.1128/JVI.02062-1010.1128/JVI.02062-10302002321068237
Search in Google Scholar Back to article
6. S. Lam, A. Lombardi and A. Ouanounou, COVID-19: A review of the proposed pharmacological treatments, Eur. J. Pharmacol.886 (2020) Article ID 173451 (11 pages); https://doi.org/10.1016/j.ejphar.2020.17345110.1016/j.ejphar.2020.173451740647732768505
Search in Google Scholar Back to article
7. Chemical Computing Group, Manual Version 2018.09, Molecular Operating Environment (MOE), Montreal 2018; http://www.chemcomp.com
Search in Google Scholar Back to article
8. G. M. Sastry, M. Adzhigirey, T. Day, R. Annabhimoju and W. Sherman, Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments, J. Comp. Aided Mol. Des. 27 (2013) 221–234; https://doi.org/10.1007/s10822-013-9644-810.1007/s10822-013-9644-823579614
Search in Google Scholar Back to article
9. R. A. Friesner, J. L. Banks, R. B. Murphy, T. A. Halgren, J. J. Klicic, D. T. Mainz, M. P. Repasky, E. H. Knoll, M. Shelley, J. K. Perry, D. E. Shaw, P. Francis, P. S. Shenkin, Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy, J. Med. Chem. 47 (2004) 1739–1749; https://doi.org/10.1021/jm030643010.1021/jm030643015027865
Search in Google Scholar Back to article
10. J. Wang, W. Wang, P. A. Kollman and D. A. Case, Automatic atom type and bond type perception in molecular mechanical calculations, J. Mol. Graph. Mod. 25 (2006) 247–260; https://doi.org/10.1016/j.jmgm.2005.12.00510.1016/j.jmgm.2005.12.00516458552
Search in Google Scholar Back to article
11. A. Jakalian, D. B. Jack and C. I. Bayly, Fast, efficient generation of high-quality atomic charges, AM1-BCC model: II. Parameterization and validation, J. Comp. Chem. 23 (2002) 1623–1641; https://doi.org/10.1002/jcc.1012810.1002/jcc.1012812395429
Search in Google Scholar Back to article
12. T. S. Lee, B. K. Allen, T. J. Giese, Z. Guo, P. Li, C. Lin, T. D. McGee, D. A. Pearlman, B. K. Radak, Y. Tao, H. Tsai, H. Xu, W. Sherman and D. M. York, Alchemical binding free energy calculations in AMBER20: Advances and best practices for drug discovery, J. Chem. Inf. Model. 2020, in press; https://doi.org/10.1021/acs.jcim.0c0061310.1021/acs.jcim.0c00613768602632936637
Search in Google Scholar Back to article
13. C. R. Guimarães and M. Cardozo, MM-GB/SA rescoring of docking poses in structure-based lead optimization, J. Chem. Inf. Model.48 (2008) 958–970; https://doi.org/10.1021/ci800004w10.1021/ci800004w18422307
Search in Google Scholar Back to article
14. J. Shao, S. W. Tanner, N. Thompson and T. E. Cheatham, Clustering molecular dynamics trajectories: 1. Characterizing the performance of different clustering algorithms, J. Chem. Theory Comp. 3 (2007) 2312–2334; https://doi.org/10.1021/ct700119m10.1021/ct700119m26636222
Search in Google Scholar Back to article
15. W. Dai, B. Zhang, X. M. Jiang, H. Su, J. Li, Y. Zhao, X. Xie, Z. Jin, J. Peng, F. Liu, C. Li, Y. Li, F. Bai, H. Wang, X. Cheng, X. Cen, S. Hu, X. Yang, J. Wang, X. Liu, G. Xiao, H. Jiang, Z. Rao, L. K. Zhang, Y. Xu, H. Yang and H. Liu, Structure-based design of antiviral drug candidates targeting the SARSCoV-2 main protease, Science368 (2020) 1331–1335; https://doi.org/10.1126/science.abb448910.1126/science.abb4489717993732321856
Search in Google Scholar Back to article

Computer-aided approaches reveal trihydroxychroman and pyrazolone derivatives as potential inhibitors of SARS-CoV-2 virus main protease

Abstract

Paradigm

My account