Intrinsic Furin-Mediated Cleavability of the Spike S1/S2 Site from SARS-CoV-2 Variant B.1.1.529 (Omicron)

The ability of SARS-CoV-2 to be primed for viral entry by the host cell protease furin has become one of the most investigated of the numerous transmission and pathogenicity features of the virus. SARS-CoV-2 The variant B.1.1.529 (Omicron) emerged in late 2020 and has continued to evolve and is now present in several distinct sub-variants. Here, we analyzed the “furin cleavage site” of the spike protein of SARS-CoV-2 B.1.1.529 (Omicron variant) in vitro, to assess the role of two key mutations (spike, N679K and P681H) that are common across all subvariants compared to the ancestral B.1 virus and other notable lineages. We observed significantly increased intrinsic cleavability with furin compared to an original B lineage virus (Wuhan-Hu1), as well as to two variants, B.1.1.7 (Alpha) and B.1.617 (Delta) that subsequently had wide circulation. Increased furin-mediated cleavage was attributed to the N679K mutation, which lies outside the conventional furin binding pocket. Our findings suggest that B.1.1.529 (Omicron variant) has gained genetic features linked to intrinsic furin cleavability, in line with its evolution within the population as the COVID-19 pandemic has proceeded.