Mutation N856K in spike reduces fusogenicity and infectivity of Omicron BA.1
Chunyun Sun, Huiyu Wang, Ji Yang, Desheng Kong, Yu-Ning Chen, Haiyue Wang, Lingling Sun, Jianbo Lu, Min Teng, Liangzhi Xie
Abstract
COVID-19 lung pathology is characterized by interstitial pneumonia with cell-cell fusion-induced syncytia and extensive tissue damage. 1 The correlation between viral fusogenicity and pathogenicity has been reported in SARS-CoV-2 variants. 2 Compared with the previous Delta or D614G variants, Omicron BA.1 has been proven to be less fusogenic and pathogenic, 3 potentially due to the high burden of mutations in spike, including 8 mutations in NTD, 15 in or adjacent to RBD, 2 in the furin-like cleavage motif (FL), and 6 in S2. However, the newly emerged Omicron sub-lineage BA.4/5 showed enhanced infectivity and fusogenicity compared to the BA.1/2. 4 It seems that progressive mutational evolution of the spike in Omicron sub-lineages leads to increased transmissibility. 5