Background & Objectives: Even after more than a year of the beginning of COVID-19 pandemic, a specific treatment for the disease has not been discovered. Vaccination programmes are being rolled out as the fastest pace possible but achievement of herd immunity will take time. Many drugs like favipiravir, remdesivir and tocilizumab are being used for the treatment of this disease but reports published by the World Health Organization and the New England Journal of Medicine shows that they do not produce any significant clinical results. In this study, by molecular docking a large set of drugs has been used to replace remdesivir in RdRp protein so that they can produce the same action and therefore provide suitable alternatives for clinical trials and emergency use.
Materials & Methods: The receptor i.e. the RdRp protein was first processed in Drug Discovery studio by removal of heterogenous atoms, water molecules, prime and template RNA strands and remdesivir. This gave us the clean RdRp molecule. Using PyRx docking software, it was converted automatically into an Autodock macromolecule. Around 750 drug molecules were loaded into PyRx using Open Babel plugin which were then converted into Autodock ligands by minimization of their energies, addition of hydrogen atoms and addition of partial charges. Using Autodock Vina ligands were docked into the restricted search space containing the target amino acids.
Results: The drugs identified in the study are saquinavir, cefoperazone, gliquidone, nelfinavir, 5-methyltetrahyrofolate among various others.
Conclusion: The drugs obtained above have also been identified in other in-silico studies as potential inhibitors of SARS-CoV2 by different mechanisms. They must be tried in-vitro because of the limitations of in-silico docking.
Key words: COVID-19; remdesivir; RdRp; saquinavir
|
