tipranavir and Coronavirus-Infections

The rapidly enlarging COVID-19 pandemic caused by the novel SARS-corona virus-2 is a global public health emergency of an unprecedented level. Unfortunately no treatment therapy or vaccine is yet available to counter the SARS-CoV-2 infection, which substantiates the need to expand research efforts in this direction. The indispensable function of the main protease in virus replication makes this enzyme a promising target for inhibitors screening and drug discovery to treat novel coronavirus infection. The recently concluded α-ketoamide ligand-bound X-ray crystal structure of SARS-CoV-2 M. For the study, we have targeted the SARS-CoV-2 M. The phylogenetic analysis of the SARS-CoV-2 genome reveals that the virus is closely related to the Bat-SL-CoV and does not exhibit any divergence at the genomic level. Molecular docking studies revealed that among the 77 drugs, screened top ten drugs shows good binding affinities, whereas the top three drugs: Lopinavir-Ritonavir, Tipranavir, and Raltegravir were undergone for molecular dynamics simulation studies for their conformational stability in the active site of the SARS-CoV-2 M. In the present study among the library of FDA approved antiviral drugs, the top three inhibitors Lopinavir-Ritonavir, Tipranavir, and Raltegravir show the best molecular interaction with the main protease of SARS-CoV-2. However, the in-vitro efficacy of the drug molecules screened in this study further needs to be corroborated by carrying out a biochemical and structural investigation.

Topics: Antiviral Agents; Betacoronavirus; Coronavirus 3C Proteases; Coronavirus Infections; COVID-19; Cysteine Endopeptidases; Drug Combinations; Drug Repositioning; Humans; Lopinavir; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Pandemics; Phylogeny; Pneumonia, Viral; Protease Inhibitors; Pyridines; Pyrones; Raltegravir Potassium; Ritonavir; SARS-CoV-2; Sulfonamides; Viral Nonstructural Proteins