An antibody-based proximity labelling map reveals mechanisms of SARS-CoV-2 inhibition of antiviral immunity. Zhang et al.
The global epidemic caused by the coronavirus SARS-CoV-2 has resulted in the infection of over 200 million people. To extend the knowledge of interactions between SARS-CoV-2 and humans, we systematically investigate the interactome of 29 viral proteins in human cells by using an antibody-based TurboID assay. In total, 1388 high-confidence human proximal proteins with biotinylated sites are identified. Notably, we find that SARS-CoV-2 manipulates the antiviral and immune responses. We validate that the membrane protein ITGB1 associates ACE2 to mediate SARS-CoV-2 entry. Moreover, we reveal that SARS-CoV-2 proteins inhibit activation of the interferon pathway through the mitochondrial protein MAVS and the methyltransferase SETD2. We propose 111 potential drugs for the clinical treatment of COVID-19 and identify three compounds that significantly inhibit the replication of SARS-CoV-2. The proximity labelling map of SARS-CoV-2 and humans provides a resource for elucidating the mechanisms of viral infection and developing drugs for COVID-19 treatment.