Potential Inhibitors of Protease 3CLpro Virus COVID-19: Drug Reposition
1Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow, 119121 Russia; *e-mail: email@example.com
2Institute of Physiologically Active Compounds, Chernogolovka 142432, Russia
Keywords:COVID-19; protease, inhibitor; drug reposition; docking; molecular dynamics
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
Figure 1. Cleavage sites of COVID-19 proteases PLpro (blue arrows) and 3CLpro (red arrows). pp1a is in yellow, pp1ab – green.
Figure 2. Structure of protease 3CLpro COVID-19. A – general view. Catalytic residues His41 and Cys145 are in yellow. B – structure of active site. Catalytic residues His41 and Cys145 are in cyan, inhibitor from pdb5R81 – magenta.
Figure 3. A distribution of quantity of ligands depend of SFD values during docking in protease 3CLpro COVID-19. The best docking solution was used for plotting.
Table 1. Drug selected as potential inhibitors of 3СLpro COVID-19 and values of their binding.
Table 2. The main pharmacological activity of selected drugs for 3СLpro COVID-19.
The work was performed in the framework of the Program for Basic Research of State Academies of Sciences for 2013-2020.
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