Abstract
The pandemic due to the novel coronavirus 2019, SARS-CoV-2, has led to a global health and economic crisis. The disease, named coronavirus disease (COVID-19), has already affected 3090445 and killed over 217769 people worldwide, as of April 30, 2020. So far, there is no specific effective medicine or vaccine against SARS-CoV-2. Several existing and approved drugs are under clinical studies for re-purposing. However, owing to the emergent situation and thereby to avoid time needed for de novo drug discovery, drug re-purposing remains to be the best option to find an effective therapeutic against the virus. Thus, the preset study was designed to evaluate potency of 82 compound/drugs in inhibiting the main protease (3CLPro) of SARS-CoV-2, using molecular docking tool. This protease is a vital enzyme for replication of the virus, and is thus a promising drug target. The analyzed compounds include 16 known protease inhibitors, two recently suggested α-ketoamides, 24 recently reported putative inhibitors, and 40 phytochemicals. The results indicate that Ritonavir, Indinavir, Montelukast, Nelfinavir, Candoxatril, Tigecycline and Lopinavir to be very potent protease inhibitors. Further, several other drugs and compounds, including phytochemicals, have been identified / predicted to be potent in inhibiting the enzyme. In addition, we hereby report relative efficacies of these compounds in inhibiting 3CLPro. Thus, the present study is significant in the therapeutic intervention of COVID-19.
Possibility of HIV-1 protease inhibitors-clinical trial drugs as repurposed drugs for SARS-CoV-2 main protease: a molecular docking, molecular dynamics and binding free energy simulation study