Molecular Mechanism of Clinically Oriented Drug Famotidine with the Identified Potential Target of SARS-CoV-2

Due to the current pandemic nature, severity, and rapid spread of COVID-19, there is eminent need to identify potential therapeutics to inhibit the novel coronavirus. In the quest, scientists from the USA had reported that the use of Famotidine in patients was associated with improved clinical outcomes and a reduced risk of intubation or death from COVID-19. However, the exact mode of action, the binding mechanism, and precise COVID-19 molecular target with which Famotidine interacts are yet to be ascertained. Here, 12 different COVID-19 protein targets have been screened against Famotidine employing molecular docking and molecular dynamics simulation. This reveals, among all the targets, the Papain-like protease (PLpro) as the potential target having the strongest affinity to Famotidine estimated to be of -7.9 kcal/mol with three hydrogen bonds. Tyrosine residue in the 268th position in the binding site seems to be very crucial for the stability of the PLpro-Famotidine complex, giving rise to multiple interactions such as hydrogen bonding as well as π-Sulfur. While the post-molecular dynamics (MD) analyses such as the root-mean-square deviation (RMSD) and fluctuation (RMSF), the radius of gyration (Rg), and the principal component analysis (PCA) affirm the stability of the complex providing an insight into the binding mechanism, the identification of a valid target PLpro of SARS-COV-2 for Famotidine would help understand its action, further development, and experimental exploration.