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.