Identification of Novel Inhibitors of SARS-CoV-2 Mpro from NCI Database by a Drug Repurposing Approach

Abstract

Background: The global spread of SARS-CoV-2 and the mortality it has caused have prompted research organizations to develop novel medications to fight against COVID-19. The main protease (Mpro) of SARS-CoV-2 is crucial to the virus’s replication and propagation in host cells. Therefore, it is a promising therapeutic target. Objectives: There are officially no certified specific drugs or available interventions for COVID-19 infection. Repurposing standard pharmaceutical drugs for COVID-19 is a promising strategy to identify potent therapeutic candidates quickly. Methods: The NCI (National Cancer Institute) database compounds, COVID-19 Mpro, and the reference ligand were prepared, and the docking, ADMET, and MMGBSA analyses were carried out using Maestro (Schrödinger Suite). Results: The study shows the results after screening NCI molecules (265,242) against COVID-19 Mpro. Compounds NCI19775, NCI226834, NCI115535, NCI270893, NCI89644, NCI332542, NCI617217, NCI43927, NCI67474, NCI250293, and NCI59266 fit in the active site of the COVID- 19 Mpro, showing a tighter interaction than the reference ligand X77. The docking score of these NCI compounds is also higher than X77. As a result, these compounds could be promising anti-COVID Mpro agents. NCI19775 (6,6-bis (benzylthio) hexane-1,2,3,4,5-pentaol)was shown to be a more potent inhibitor of COVID-19 main protease, and the outcomes also exhibit the potential for NCI compounds to interact with COVID Mpro. Conclusions: Our computational strategy identified promising and efficacious SARS-CoV-2 inhibitors that could be investigated further in clinical trials.