Abstract
Additional mutations in the viral Spike protein helped the BA.2.12.1 and BA.4/5 SARS-CoV-2 Omicron subvariants to outcompete the parental BA.2 subvariant. Here, we determined the functional impact of mutations that newly emerged in the BA.2.12.1 (L452Q, S704L) and BA.4/5 (Δ69-70, L452R, F486V, R493Q) Spike proteins. Our results show that mutation of L452Q/R or F486V typically increases and R493Q or S704L impair BA.2 Spike-mediated infection. In combination, changes of Δ69-70, L452R, and F486V contribute to the higher infectiousness and fusogenicity of the BA.4/5 Spike. L452R/Q and F486V in Spike are mainly responsible for reduced sensitivity to neutralizing antibodies. However, the combined mutations are required for full infectivity, reduced TMPRSS2 dependency, and immune escape of BA.4/5 Spike. Thus, it is the specific combination of mutations in BA.4/5 Spike that allows increased functionality and immune evasion, which helps to explain the temporary dominance and increased pathogenicity of these Omicron subvariants.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
