Warning: This is a preliminary report that has not been peer-reviewed. It should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information.

SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant (Preliminary Report)

Recent studies have revealed the unique virological characteristics of Omicron, the newest SARS-CoV-2 variant of concern, such as pronounced resistance to vaccine-induced neutralizing antibodies, less efficient cleavage of the spike protein, and poor fusogenicity. However, it remains unclear which mutation(s) in the spike protein determine the virological characteristics of Omicron. ...
Here, we show that the representative characteristics of the Omicron spike are determined by its receptor-binding domain. Interestingly, the molecular phylogenetic analysis revealed that the acquisition of the spike S375F mutation was closely associated with the explosive spread of Omicron in the human population. We further elucidate that the F375 residue forms an interprotomer pi-pi interaction with the H505 residue in another protomer in the spike trimer, which confers the attenuated spike cleavage efficiency and fusogenicity of Omicron. Our data shed light on the evolutionary events underlying Omicron emergence at the molecular level.HighlightsO_LIOmicron spike receptor binding domain determines virological characteristicsC_LIO_LISpike S375F mutation results in the poor spike cleavage and fusogenicity in OmicronC_LIO_LIAcquisition of the spike S375F mutation triggered the explosive spread of OmicronC_LIO_LIF375-H505-mediated {pi}-{pi} interaction in the spike determines the phenotype of OmicronC_LI
Date: Apr. 03, 2022
Status: Preliminary Report
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