Structural insights of key enzymes into therapeutic intervention against SARS-CoV-2

COVID-19 pandemic, caused by SARS-CoV-2, has drastically affected human health all over the world. After the emergence of the pandemic the major focus of efforts to attenuate the infection has been on repurposing the already approved drugs to treat COVID-19 adopting a fast-track strategy. However, to date a specific regimen to treat COVID-19 is not available. Over the last few months a substantial amount of data about the structures of various key proteins and their recognition partners involved in the SARS-CoV-2 pathogenesis has emerged. These studies have not only provided the molecular level descriptions of the viral pathogenesis but also laid the foundation for rational drug design and discovery. In this review, we have recapitulated the structural details of four key viral enzymes, RNA-dependent RNA polymerase, 3-chymotrypsin like protease, papain-like protease and helicase, and two host factors including angiotensin-converting enzyme 2 and transmembrane serine protease involved in the SARS-CoV-2 pathogenesis, and described the potential hotspots present on these structures which could be explored for therapeutic intervention. We have also discussed the significance of endoplasmic reticulum a-glucosidases as potential targets for anti-SARS-CoV-2 drug discovery.