Potential inhibitors of protease 3CLpro virus COVID-19: drug reposition


  • V.S. Skvortsov Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia; Institute of Physiologically Active Compounds, Chernogolovka 142432, Russia
  • D.S. Druzhilovskiy Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia
  • A.V. Veselovsky Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia; Institute of Physiologically Active Compounds, Chernogolovka 142432, Russia




molecular dynamics; docking; drug reposition; inhibitor; protease; COVID-19


Pneumonia caused by the COVID-19 virus has led to quick search of drugs that would able to block the spread of this virus. A standard way of drug development is a long process. One approach that can significantly accelerate drug development is drug reposition. In this study a virtual screening of the database of approved drugs has been used for search inhibitors against 3СLpro COVID-19, the main protease of COVID-19. Molecular docking, simulation of molecular dynamics and binding energy estimation by MM-GBSA method allowed to select several compounds for further experimental testing. The most promising drugs are the HIV protease inhibitor Indinavir, the inhibitor of protease hepatitis C Telaprevir, the antiulcer drug Dalargin, and the ErB receptor tyrosine kinase inhibitor Neratinib


  1. Cui, J., Li, F., Shi, Z.L. (2019) Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol., 17(3), 181-192. DOI
  2. de Wit, E., van Doremalen, N., Falzarano, D., Munster, V.J. (2016) SARS and MERS: recent insights into emerging coronaviruses. Nat. Rev. Microbiol., 14(8), 523-534. DOI
  3. Zhou, P., Yang, X.L., Wang, X.G., Hu, B., Zhang, L., Zhang, W., Si, H.R., Zhu, Y., Li, B., Huang, C.L., Chen, H.D., Chen, J., Luo, Y., Guo, H., Jiang, R.D., Liu, M.Q., Chen, Y., Shen, X.R., Wang, X., Zheng, X.S., Zhao, K., Chen, Q.J., Deng, F., Liu, L.L., Yan, B., Zhan, F.X., Wang, Y.Y., Xiao, G.F., Shi, Z.L. (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798), 270-273. DOI
  4. Wu, F., Zhao, S., Yu, B., Chen, Y.M., Wang, W., Song, Z.G., Hu, Y., Tao, Z.W., Tian, J.H., Pei, Y,Y., Yuan, M.L., Zhang, Y.L., Dai, F.H., Liu, Y., Wang, Q.M., Zheng, J.J., Xu, L., Holmes, E.C., Zhang, Y.Z. (2020) A new coronavirus associated with human respiratory disease in China. Nature, 579(7798), 265-269. DOI
  5. Hegyi, A., Ziebuhr, J. (2002) Conservation of substrate specificities among coronavirus main proteases. J. Gen. Virol.. .83(Pt 3), 595-599. DOI
  6. Pillaiyar, T., Manickam, M., Namasivayam, V., Hayashi, Y., Jung, S.H. (2016) An Overview of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy. J. Med. Chem., 59(14), 6595-6628. DOI
  7. Gautret, P., Lagier, J.C., Parola, P., Hoang, V.T., Meddeb, L., Mailhe, M., Doudier, B., Courjon, J., Giordanengo, V., Vieira, V.E., Dupont, H.T., Honoré, S., Colson, P., Chabrière, E., La Scola, B., Rolain, J.M., Brouqui, P., Raoult, D. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int. J. Antimicrob. Agents, 105949. DOI
  8. Novac, N. (2013) Challenges and opportunities of drug repositioning. Trends Pharmacol. Sci., 34(5), 267-272. DOI
  9. Jin, G., Wong, S.T. (2014) Toward better drug repositioning: prioritizing and integrating existing methods into efficient pipelines. Drug Discov. Today, 19(5), 637-644. DOI
  10. Pushpakom, S., Iorio, F., Eyers, P.A., Escott, K.J., Hopper, S., Wells, A., Doig, A., Guilliams, T., Latimer, J., McNamee, C., Norris, A., Sanseau, P., Cavalla, D., Pirmohamed, M. (2019) Drug repurposing: progress, challenges and recommendations. Nat. Rev. Drug Discov., 18(1), 41-58. DOI
  11. Ashburn, T.T., Thor, K.B. (2004) Drug repositioning: identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov., 3(8), 673-683. DOI
  12. Gupta, S.C., Sung, B., Prasad, S., Webb, L.J., Aggarwal, B.B. (2013) Cancer drug discovery by repurposing: teaching new tricks to old dogs. Trends Pharmacol. Sci., 34(9), 508-517. DOI
  13. Tobinick, E.L. (2009) The value of drug repositioning in the current pharmaceutical market. Drug News Perspect., 22(2), 119-125. DOI
  14. Baek, M.C., Jung, B., Kang, H., Lee, H.S., Bae, J.S. (2015) Novel insight into drug repositioning: Methylthiouracil as a case in point. Pharmacol. Res., 99, 185-193. DOI
  15. Khan, R.J., Jha, R.K., Amera, G., Jain, M., Singh, E., Pathak, A., Singh, R.P., Muthukumaran, J., Singh, A.K. (2020) Targeting SARS-CoV-2: A Systematic Drug Repurposing Approach to Identify Promising Inhibitors Against 3C-like Proteinase and 2'-O-RiboseMethyltransferase. J. Biomol. Struct. Dyn. DOI
  16. Kandeel, M., Al-Nazawi, M. (2020) Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease. Life Sci. DOI
  17. Ortega, J.T., Serrano, M.L., Pujol, F.H., Rangel, H.R. (2020) Unrevealing sequence and structural features of novel coronavirus using in silico approaches: The main protease as molecular target. EXCLI J., 19, 400-409. DOI
  18. Shah, B., Modi, P., Sagar, S.R. (2020) In silico studies on therapeutic agents for COVID-19: Drug repurposing approach. Life Sci., 252, 117652. DOI
  19. Balius, T.E., Mukherjee, S., Rizzo, R.C. (2011) Implementation and evaluation of a docking-rescoring method using molecular footprint comparisons. J. Comput. Chem., 32(10), 2273-2289. DOI
  20. Humphrey, W., Dalke, A., Schulten, K. (1996) VMD: visual molecular dynamics. J. Mol. Graph., 14(1),:33-38. DOI
  21. Ghosh, A.K., Osswald, H.L., Prato, G. (2016) Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS. J. Med. Chem., 59(11), 5172-5208. DOI
  22. McCauley, J.A., Rudd, M.T. (2016) Hepatitis C virus NS3/4a protease inhibitors. Curr. Opin. Pharmacol., 30, 84-92. DOI
  23. Retrieved April 7, 2020, from: http://fmbaros.ru/press-tsentr/novosti/detail/?ELEMENT_ID=38187
  24. Singh, J., Petter, R.C., Baillie, T.A., Whitty, A. (2011) The resurgence of covalent drugs. Nat. Rev. Drug Discov., 10(4), 307-317. DOI



How to Cite

Skvortsov, V., Druzhilovskiy, D., & Veselovsky, A. (2020). Potential inhibitors of protease 3CLpro virus COVID-19: drug reposition. Biomedical Chemistry: Research and Methods, 3(1), e00124. https://doi.org/10.18097/BMCRM00124