SARS-CoV-2 S protein disrupts the formation of ISGF3 complex through conserved S2 subunit to antagonize type I interferon response

Abstract

This study unveils a new mechanism by which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein attenuates the host’s antiviral immune response. The interferon-inhibitory mechanism of the S protein was universal among SARS-CoV-2 variants and other human coronaviruses, including SARS-CoV, MERS-CoV, HCoV-229E, HCoV-NL63, and HCoV-HKU1, through conserved S2 domains. Our study expands the understanding of SARS-CoV-2 and other human coronaviruses in evading antiviral immune strategies, which is very important for the design and optimization of vaccine antigens, thus providing a theoretical basis for human anti-coronavirus immunity and understanding the interaction between the host and coronavirus.