Structure genomics of SARS-CoV-2 and its Omicron variant: drug design templates for COVID-19

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and persistently threatens to humanity. With tireless efforts from scientists around the world, understanding of the biology of coronavirus has been greatly enhanced over the past 2 years. Structural biology has demonstrated its powerful impact on uncovering structures and functions for the vast majority of SARS-CoV-2 proteins and guided the development of drugs and vaccines against COVID-19. In this review, we summarize current progress in the structural biology of SARS-CoV-2 and discuss important biological issues that remain to be addressed. We present the examples of structure-based design of Pfizer's novel anti-SARS-CoV-2 drug PF-07321332 (Paxlovid), Merck's nucleotide inhibitor molnupiravir (Lagevrio), and VV116, an oral drug candidate for COVID-19. These examples highlight the importance of structure in drug discovery to combat COVID-19. We also discussed the recent variants of Omicron and its implication in immunity escape from existing vaccines and antibody therapies.

Automated summary

The tireless efforts of scientists globally have greatly enhanced our understanding of the biology of coronaviruses, with structural biology playing a key role in uncovering structures and functions of viral proteins and guiding drug and vaccine development. The importance of structure in drug discovery to combat COVID-19 has been highlighted, while attention is needed on the implications of Omicron variants on existing vaccines and antibody therapies.