Computational Insights into the Drug Repurposing and Synergism of FDA-approved Influenza Drugs Binding with SARS-CoV-2 Protease against COVID-19

Abstract

The concept of drug repurposing is extensively used currently to identify already approved/under investigation/discarded potential drugs for various other diseases, owing to the fact that many drugs could have multiple protein targets and many diseases share overlapping molecular pathways. The geographical spread of COVID-19 infections originating from Wuhan, China, has provided an opportunity to study the natural history of the recently emerged virus. The source of the SARS-CoV-2 is yet not known, even though the initial cases have been connected with the Huanan South China Seafood Market. In this study, the bioactivity of FDA-approved influenza drugs (Baloxavir, Oseltamivir, Peramivir and Zanamivir) were evaluated as inhibitors for COVID-19 using computational modeling approaches. The nominated drugs were docked on SARS-CoV-2 main protease (PDB ID: 6LU7) and also with SARS HCoV (PDB ID: 6NUR) for comparison, to evaluate the binding affinity of these drugs. ADMET and DFT analyses were also further carried out to analyze the potential of these influenza drugs as an effective inhibitor against COVID-19. The DFT calculations were performed to estimate the thermal parameters, dipole moment of the investigated drugs; additionally, chemical reactivity descriptors were investigated. The results of molecular docking with respect to binding energies in Kcal/mol suggested that binding affinity of influenza drugs with SARS-CoV-2 was in the order Zanamivir > Baloxavir > Oseltamivir > Peramivir. The findings of this study can facilitate rational drug design targeting the SARS-Cov-2 main protease.