PSGL-1 blocks SARS-CoV-2 S protein-mediated virus attachment and infection of target cells

P-selectin glycoprotein ligand-1 (PSGL-1) is a cell surface glycoprotein that binds to P-, E-, and L-selectins to mediate the tethering and rolling of immune cells on the surface of the endothelium for cell migration into inflamed tissues. PSGL-1 has been identified as an interferon-γ (INF-γ)-regulated factor that restricts HIV-1 infectivity, and has recently been found to possess broad-spectrum antiviral activities. Here we report 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 findings suggest that PSGL-1-imprinted non-infectious viral particles could serve as a live attenuated vaccine for SARS-CoV-2 infection.