Pathology

Epitope

Virus

Disease

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Biology

Gene

Biophysics

Infectivity

Peptide sequence

Antibody

Virology

Coronavirus

Cell biology

Immune escape

Genetics

Medicine

Immune system

Cell

The SARS-CoV-2 Omicron variant with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the spike (S) from Omicron reveals amino acid substitutions forging interactions that stably maintain an active conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of the viral fusion step. Alterations in local conformation, charge, and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD- and RBD-antibodies, facilitating viral immune escape. Structure of the Omicron S bound with human ACE2, together with the analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members, as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies, sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics.

Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron