In-silico Screening of Some Important Bioactive Compounds as Potential Inhibitors of 3CLpro Protein of SARS-CoV-2 and MERS-CoV Virus

DOI:

https://doi.org/10.37285/ijpsn.2022.15.4.4

Authors

  • Chandreyi Ghosh Department of Biotechnology, Techno India University, West Bengal, India.
  • Moumita Saha Department of Biotechnology, Techno India University, West Bengal, India.
  • Sohini Kulavi Department of Biotechnology, Maulana Abul Kalam Azad University of Technology, West Bengal, India.
  • Sirshendu Chatterjee Department of Biotechnology, Techno India University, West Bengal, India.

Abstract

Background: Coronavirus (SARS-CoV-2), the leading cause of the epidemic in 2019, also known as COVID-19, has raised ongoing global concerns. The most favourable target protein for this flu is 3CLpro (conserved 3-chymotrypsin-like protease), also known as Mpro. Covaxin and Covishield vaccination is going in India. Remdesivir, as well as some antimalarial drugs such as Hydroxychloroquine and Chloroquine, are used for extreme necessity. However, Hydroxychloroquine and Chloroquine and their derivatives are not convenient for those who are suffering from hypertension, diabetes, cardiac arrest, and many more. 

Objective: Here, we choose some bioactive compounds for docking studies with the Mpro of SARS CoV2 and MERS as it is used as the primary target for a comparative study. 

Methods: The docking process was carried out by preparing both 3CLpro proteins, i.e., 2YNA and 6LU7, and then the ligand molecules were downloaded from Pubchem, DrugBank, and Zinc15 databases. Furthermore, SwissAdme and pkCSM software were used for the determination of toxicity and Pharmacokinetic properties (ADMET) properties. Lastly, docking was carried out by the Autodock version 4.2 program, and the docking score was compared to the reference inhibitor Ritonavir. 

Results: Among 17 bioactive compounds used for docking studies, Quercetin, Trans-Resveratol, Kaemferol, and Theaflavin have top, binding affinity for target proteins, i.e., Theaflavin (-14.35 kcal/mol), Quercetin (-11.88kcal/mol), Kaempferol (-9.3 kcal/mol) and Trans-Resveratol (-9.31 kcal/mol) and also obey Lipinski's rule which makes them potential drug candidate against Covid-19 virus. Hence, the application of these plant-based bioactive compounds alone or along with scheduled vaccination may be the best therapeutic approach in the current scenario.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Keywords:

ADMET, AutoDock4., Bioactive Compounds, Covid-19 Virus, MERS-CoV, In-Silico Docking

Downloads

Published

2022-09-15

How to Cite

1.
Ghosh C, Saha M, Kulavi S, Chatterjee S. In-silico Screening of Some Important Bioactive Compounds as Potential Inhibitors of 3CLpro Protein of SARS-CoV-2 and MERS-CoV Virus. Scopus Indexed [Internet]. 2022 Sep. 15 [cited 2024 Dec. 22];15(4):6043-54. Available from: https://ijpsnonline.com/index.php/ijpsn/article/view/3032

Issue

Vol. 15 No. 4 (2022): July-August 2022

Section

Research Articles
Crossref
Scopus
Google Scholar
Europe PMC

References

Anand K, Ziebuhr J, Mesters JR, Wadhwani P and Hilgenfeld R. (2003). Coronavirus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs. Science 300(5626): 1763–1767.

BIOVIA, Dassault Systèmes, [Discovery Studio Client], [2020], San Diego: Dassault Systèmes, [2020]

Chen,Y.W, Yiu, C.P.B. and Wong, K.Y. (2020).Prediction of the SARSCoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: Virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates. F1000Research 9(129).

Daina, A., Michielin, O. and Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports 7(42717).

Dong, E., Du, H. and Gardner, L. (2020). An interactive web-based dashboard to track COVID-19 in real time. The Lancet Infectious Diseases 20(5): 533-534.

Enmozhi, K.S., Raja, K., Sebastine, I. and Joseph, J. (2020). Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach. Journal of biomolecular structure and dynamics 39(9): 3092-3098.

Falade, A.V., Adelusi, I.T., Adedotun, O. I., Hammed, A.M., Lawal, AT and Agboluaje, A. S (2021) In silico investigation of saponins and tannins as potential inhibitors of SARS‑CoV‑2 main protease (Mpro). In Silico Pharmacology 9(9):2-15.

Guan,W. J., Ni, Z. Y., Hu, Y., Liang, Ou, C. Q., He, J. X., W. H., Liu, L., Shan,H., Lei, C. L. and Hui, D. (2020). China Medical Treatment Expert Group for Covid-19. Clinical characteristics of Coronavirus disease 2019 in China. The New England Journal of Medicine 382: 1708-1720.

Gyebi, A.G., Ogunro, B.O., Adegunloye, P.A., Ogunyemi, M.O., and Afolabi, O.S. (2020). Potential inhibitors of coronavirus 3-chymotrypsin-like protease (3CLpro): an in silico screening of alkaloids and terpenoids from African medicinal plants. Journal of Biomolecular Structure and Dynamics 39(9): 3396-3408.

Guastalegname, M., and Vallone, A. (2020). Could chloroquine/ Hydroxychloroquine be harmful in coronavirus disease 2019 (COVID-19) treatment? Clinical Infectious Diseases 71(15): 888-889.

Gautret, P., Lagier, J., Parola, P., Mailhe, M., Hoang, V. T., Meddeb, L., Doudier, B., Courjon, J., Giordanengo, V., and Vieira, V. E. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents 56(1): 105949.

Guo,Y., Cao, Q., Hong, Z., Tan, Y., Jin, H., Chen, S., Wang, D., Tan, K., and Yan, Y. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Military Medical Research 7(11).

Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., and Gu, X. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan. The Lancet, 395(10223): 497–506.

Irwin J.J., Sterling T., Mysinger M.M., Bolstad E.S. & Coleman R.G. (2012). ZINC: A Free Tool to Discover Chemistry for Biology. J. Chem. Inf. Model 52(7): 1757-1768.

Khan N, and Mukhtar H. (2013). Tea and Health: Studies in Humans. Curr Pharm Des 19(34): 6141–6147.

López-Blanco JR., Garzón JI., Chacón P. (2011) iMod: multipurpose normal mode analysis in internal coordinates. Bioinformatics. 27 (20): 2843-2850

Nickel, J., Gohlke, B.-O., Erehman, J., Banerjee, P., Goede, A., Dunkel, M., Rong, W. W., and Preissner, R. (2014). SuperPred: Update on drug classification and target prediction. Nucleic Acids Research42(Web Serverissue): W26–31.

O’Boyle N.M., Banck, M., Morley, C., James, C. A., Vandermeersch, T., & Hutchison, G. R. (2011). Open Babel: An open chemical toolbox. Journal of Cheminformatics 3(33).

Pires, D.E., Blundell, T.L., and Ascher, D. B. (2015). PkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry58(9): 4066–4072.

Pelz ,N. F., Bian, Z., Zhao, B., Shaw, S., Belmar, J., Tarr, J. C., Gregg, C., Camper, D. V., Goodwin, C. M., Arnold, A. L. and Sensintaffar, J. L. (2016). Discovery of 2-indole-acylsulfonamide myeloid cell leukemia 1 (Mcl-1) inhibitors using fragment-based methods. J. Med. Chem 59(5): 2054–2066.

Rehan, M., & Shafiullah. (2021). Medicinal plant-based saponins targeting COVID-19 M pro in silico, Traditional Medicine Research 6(24).

Saha M, Roychowdhuri I, Ghosh C, Kulavi S, Chakraborty A, Roy A and Chatterjee S (2021). Medicinal herbs and its bioactive ingredients: The alternative green resources against viruses. J Pharmacogn Phytochem 10(6):372-378.

Seresht, R.H., Cheshomi, H., Falanji, F., Motlagh, M. F., Hashemian, M., and Mireskandari, E. (2019). Cytotoxic activity of caffeic acid and gallic acid against MCF-7 human breast cancer cells: An in silico and in vitro study. Avicenna J Phytomed 9(6): 574-586.

Singh S, Gupta AK and Verma A. (2013). Molecular properties and bioactivity score of the Aloe vera antioxidant compounds-in order to lead finding. Res J Pharm Biol Chem Sci. 4:876-81.

Sterling T and Irwin J.J. (2015). ZINC 15 – Ligand Discovery for Everyone. J. Chem. Inf. Model 55(11): 2324–2337

Souers, A.J., Leverson, J. D., Ackler, S. L., Boghaert, E. R., Catron, N. D.,Chen, J., Dayton, B. D., Ding, H., Enschede, S. H., Fairbrother, W. J. and Huang, D. C. S. (2013). ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nature Medicine 19(2): 202–208

Sarma, P., Sekhar, N., Prajapat, M., Kaur, H., Avti, P., Kumar, S., Singh, S.,Kumar, H., Prakash, A., Dhibar, D. P., and Medhi, B. (2020). In-silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain). Journal of Biomolecular Structure and Dynamics 1–9.

Wang,D., Wang, D., Hu, B., Zhu, F., Hu, C., Liu, X., Zhang, J., Wang, B., Xiang, H., Xiong, Y.and Zhao, Y. (2020). Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 323(11): 1061-1069.

Wishart, D.S., Knox, C., Guo, A. C., Shrivatava, S., Hassanali, M., Stothard, P., chang, Z., and Woolsey, Z. (2006). DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res1(34) (Database issue): D668-72.

Willard, L., Ranjan, A., Zhang, H., Monzavi, H., Boyko, F R., Sykes, D B., and Wishart, S D. (2003). "VADAR: a web server for quantitative evaluation of protein structure quality" Nucleic Acids Res 31(13): 3316–3319.

Wu, C., Liu, Y., Yang, Y., Zhong, W., Wang, Y., Zhang, P., Wang, Q., Li, M., Li, X., Xu, Y., Zheng, M., Chen, L., and Li, H. (2020). Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B 10(5):766-788.

Zhu, N., Zhang, D., Li, X., Wang, W., Yang, B., Zhao, X., Song, J., Huang, B., Shi, W., Lu, R. and Niu, P. (2020). A novel coronavirus from patients with pneumonia in China. 2019. The New England Journal of Medicine 382(8):727–733.

Zhou, P., Wang, X.-G., Hu, B., Yang, X.-L., Zhang, L., Zhang, W., Si, H.-R., Zhu, Huang, C.-L., Y., Li, B., and Chen, H.-D. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(7798): 270–273.