PROS1 and infection: We find that the SARS-CoV-2 HRC-derived cholesterol conjugate potently inhibits fusion mediated by the SARS-CoV-2 S protein, blocks infection of cultured cells by live SARS-CoV-2 and MERS-CoV, and inhibits the spread of SARS-CoV-2 in human airway epithelia (HAE).