The use of US FDA-approved drugs is preferred due to the need for lower costs and less time. In in silico
medicine, repurposing is a quick and accurate way to screen US
FDA-approved medications to find a therapeutic option for COVID-19
infection. Dual inhibitors possess dual inhibitory activity, which may
be due to the inhibition of two different enzymes, and are considered
better than combination therapy from the developmental and clinical
perspectives. In this study, a molecular docking simulation was
performed to identify the interactions of antiviral drugs with the
critical residues in the binding site of the main SARS-CoV-2 protease,
spike glycoprotein, and papain-like protease receptors compared to the
angiotensin-converting enzyme-related carboxypeptidase (ACE2) receptor
of host cells. Each of the receptors was docked with 70 US FDA-approved
antiviral drugs using AutoDock Vina. A molecular dynamics (MD)
simulation study was also used for 100 ns to confirm the stability
behaviour of the ligand receptor complexes. Among the drugs that had the
strongest interaction with the SARS-CoV-2 main protease, spike
glycoprotein and papain-like protease receptors, and host cell ACE2
receptors, Simeprevir, Maraviroc and Saquinavir had dual inhibitory
effects. The MD simulation study confirmed the stability of the
strongest interactions between the antiviral drugs and the main
protease, ACE2, spike glycoprotein, and papain-like protease receptors
to 100 ns. However the results of MMPBSA analysis showed that the bond
between Saquinavir and the ACE2 receptor was weak. Simeprevir and
Maraviroc drugs had acceptable binding energies with dual receptors,
especially the Simeprevir.Communicated by Ramaswamy H. Sarma.