Computational modeling of the complex between glycyrrhizin and SARS-CoV-2 protease 3CLpro as a target for the development of antiviral drugs
DOI:
https://doi.org/10.15407/dopovidi2022.01.115Keywords:
COVID-19, drug design, SARS-CoV-2, 3CLpro proteinase, glycyrrhizin, dockingAbstract
The basic proteinase of SARS-CoV-2 Mpro virus (3CLpro) controls a number of activities of the replication complex of the virus and is therefore a target for the development of specific inhibitors. In the development of drugs against SARS-CoV-2, much attention is paid to previously known effective compounds. One such compound may be glycyrrhizin, a triterpenoid saponin isolated from licorice root (Glycyrrhizae radix). In this work we performed the computer simulations of the glycyrrhizin complex with the SARS-CoV-2 protease in order to study the mechanism of glycyrrhizin binding in the protease active site and the possible inhibition of catalytic activity of this enzyme. Molecular docking of glycyrrhizin was performed on the structure of 3CLpro SARS-CoV-2 protease with an open catalytic loop obtained from the trajectory of molecular dynamics at 694 ns simulation time. Binding energy for the preferred structural complex of glycyrrhizin was found as −10. 723 kcal/mol, with glycyrrhizin forming 9 hydrogen bonds with amino acids residues Thr26, Asn119, Asn142, Glu166, Arg188 and Gln189 of protease.
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Rothan, H. A. & Byrareddy, S. N. (2020). The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J. Autoimmun., 109, 102433. https: //doi. org/10. 1016/j. jaut. 2020. 102433
Liu, C., Zhou, Q., Li, Y., Garner, L. V., Watkins, S. P., Carter, L. J., Smoot, J., Gregg, A. C., Daniels, A. D., Jervey, S. & Albaiu, D. (2020). Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Cent. Sci., 6, No. 3, pp. 315-331. https: //doi. org/10. 1021/acscentsci. 0c00272
Ksiazek, T. G, Erdman, D., Goldsmith, C. S., Zaki, S. R., Peret, T., Emery, S., Tong, S., Urbani, C., Comer, J. A., Lim, W., Rollin, P. E., Dowell, S. F., Ling, A. -E., Humphrey, C. D., Shieh, W. -J., Guarner, J., Paddock, C. D., Rota, P., Fields, B., DeRisi, J., Yang, J. -Y., Cox, N., Hughes, J. M., LeDuc, J. W., Bellini, W. J., Anderson, L. J., SARS Working Group. (2003). A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med., 348, pp. 1953-1966. https: //doi. org/10. 1056/NEJMoa030781
Odynets, K. A. & Kornelyuk, A. I. (2003). Molecular aspects of organization and expression of SARS-CoV coronavirus genome. Biopolym. Cell, 19, No. 5, pp. 414-431 (in Ukrainian). https: //doi. org/10. 7124/bc. 00066F
Anand, K., Palm, G. J., Mesters, J. R., Siddell, S. G., Ziebuhr, J. & Hilgenfeld, R. (2002). Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain. EMBO J., 21, No. 13, pp. 3213-3224. https: //doi. org/10. 1093/emboj/cdf327
Zhang, L., Lin, D., Sun, X., Curth, U., Drosten, C., Sauerhering, L., Becker, S., Rox, K. & Hilgenfeld, R. (2020). Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science, 368, pp. 409-412. https: //doi. org/10. 1126/science. abb3405
Kneller, D. W., Phillips, G., O’Neill, H. M., Jedrzejczak, R., Stols, L., Langan, P., Joachimiak, A., Coates, L. & Kovalevsky, A. (2020). Structural plasticity of SARS-CoV-2 3CL M(pro) active site cavity revealed by room temperature X-ray crystallography. Nat. Commun., 3202. https: //doi. org/10. 1038/s41467-020-16954-7
Cinatl, J., Morgenstern, B., Bauer, G., Chandra, P., Rabenau, H. & Doerr, H. W. (2003). Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 361, No. 9374, pp. 2045-2046. https: //doi. org/10. 1016/S0140-6736(03)13615-X
Pastorino, G., Cornara, L., Soares, S., Rodrigues, F. & Oliveira, M. B. P. P. (2018). Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review. Phytother. Res., 32, No. 12, pp. 2323-2339. https: // doi. org/10. 1002/ptr. 6178
Wang, C., Horby, P. W., Hayden, F. G. & Gao, G. F. (2020). A novel coronavirus outbreak of global health concern. Lancet, 395, No. 10223, pp. 470-473 https: //doi. org/10. 1016/S0140-6736(20)30185-9
Harder, E., Damm, W., Maple, J., Wu, C., Reboul, M., Xiang, J. Y., Wang, L., Lupyan, D., Dahlgren, M. K., Knight, J. L., Kaus, J. W., Cerutti, D. S., Krilov, G., Jorgensen, W. L., Abel, R. & Friesner, R. A. (2016). OPLS3: A force field providing broad coverage of drug-like small molecules and proteins. J. Chem. Theory Comput., 12, No. 1, pp. 281-296. https: //doi. org/10. 1021/acs. jctc. 5b00864
Shaw, D. E. (2020). Molecular dynamics simulations related to SARS-CoV-2. D. E. Shaw Research Technical Data. Retrieved from http: //www. deshawresearch. com/resources_sarscov2. html
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