COVID-19, which has emerged recently as a pandemic viral infection caused by SARS-coronavirus 2 has spread rapidly around the world, creating a public health emergency . The current situation demands an effective therapeutic strategy to control the disease using drugs that are approved, or by inventing new ones . The present study examines the possible repurposing of existing anti-viral protease inhibitor drugs . For this, the structural features of the viral spike protein, the substrate for host cell protease and main protease of the available SARS CoV-2 isolates were established by comparing with related viruses for which antiviral drugs are effective . The results showed 97% sequence similarity among SARS and SARS-CoV-2 main protease and has same cleavage site positions and ACE2 receptor binding region as in the SARS-CoV spike protein . Though both are N-glycosylated, unlike SARS-CoV, human SARS-CoV-2 S-protein was O-glycosylated as well . Molecular docking studies were done to explore the role of FDA approved protease inhibitors to control SARS-CoV-2 replication . The results indicated that, Ritonavir has the highest potency to block SARS-CoV-2 main protease and human TMPRSS2, a host cell factor that aids viral infection . Other drugs such as Indinavir and Atazanavir also showed favourable binding with Cathepsin B/L that helped viral fusion with the host cell membrane . Further molecular dynamics simulation and MM-PBSA binding free energy calculations confirmed the stability of protein-drug complexes . These results suggest that protease inhibitors particularly Ritonavir, either alone or in combination with other drugs such as Atazanavir, have the potential to treat COVID 19 . Communicated by Ramaswamy H. Sarma.