Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant

Abstract The emergence of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Omicron, is the most urgent concern in the global health in December 2021. Our statistical modelling estimates that Omicron is >3.0-fold and >5.6-fold more transmissible than Delta in South Africa and the UK, respectively. Intriguingly, cell culture experiments show that Omicron is less fusogenic than Delta and ancestral SARS-CoV-2. Although the spike (S) protein of Delta is efficiently cleaved into the two subunits, which facilitates cell-cell fusion, Omicron S is faintly cleaved. Further, in hamster model, Omicron shows decreased lung infectivity and is less pathogenic compared to Delta and ancestral SARS-CoV-2. Our data suggest that the efficacy of SARS-CoV-2 S cleavage and viral fusogenicity are closely associated with viral pathogenicity, and Omicron evolved to exhibit increased transmissibility and attenuated pathogenicity.