Antagonism of Coronavirus Spike Proteins by Cellular Host Factors

Division Of Basic Sciences - Nci

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Abstract

In a structural and functional analysis of the SARS-CoV-2 S protein that we recently started, we have determined that MARCH8, but not a catalytically inactive MARCH8 mutant, targets the S proteins of SARS-CoV, MERS-CoV, and SARS-CoV-2 for degradation. We also showed that human airway epithelial cells express MARCH8 upon treatment with IFN. The work on MARCH protein-mediated antagonism may reveal new opportunities for therapeutic intervention with S protein trafficking and incorporation into virus particles. This work was recently published (mBio 12: e00219-21, 2021). _____In a separate study, we showed that virion incorporation of PSGL-1 on SARS-CoV and SARS-CoV-2 pseudovirions blocks S protein-mediated virus attachment and infection of target cells. These results demonstrate that PSGL-1 can serve as an IFN-regulated host factor that restricts CoV infectivity. This work was recently published (Viruses 13: 46, 2020). _____We are now focusing on defining the mechanism by which MARCH E3 ubiquitin ligases antagonize the SARS-CoV-2 S protein, evaluating the antiviral activity of GBP ATPases against the SARS-CoV-2 S protein, and measuring the expression of host cell anti-SARS-CoV-2 S protein antagonists in relevant cell types.