Summary
The global epidemic caused by the coronavirus severe acute respiratory syndrome coronavirus-2 (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, 1,388 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 angiotensin-converting enzyme 2 (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 mitochondrial antiviral-signaling protein (MAVS) and the methyltransferase SET domain containing 2, histone lysine methyltransferase (SETD2). We propose 111 potential drugs for the clinical treatment of coronavirus disease 2019 (COVID-19) and identify three compounds that significantly inhibit the replication of SARS-CoV-2. The proximity labeling map of SARS-CoV-2 and humans provides a resource for elucidating the mechanisms of viral infection and developing drugs for COVID-19 treatment.
【저자키워드】 COVID-19, SARS-CoV-2, interactome, TurboID, proximity labeling, 【초록키워드】 Treatment, coronavirus disease, viral infection, ACE2, coronavirus, Antiviral, knowledge, Human, Infection, drug, angiotensin-converting enzyme 2, Protein, Epidemic, membrane protein, humans, methyltransferase, immune responses, pathway, lysine, resource, mechanism, Coronavirus-2, Interaction, MAVS, Clinical treatment, mitochondrial, acute respiratory syndrome, Activation, Viral protein, SARS-CoV-2 entry, Compound, domain, ITGB1, SARS-CoV-2 protein, human cell, labeling, replication of SARS-CoV-2, SETD2, identify, caused, significantly, inhibit, provide, the interferon, proximal, biotinylated, mitochondrial antiviral-signaling protein, SET, 【제목키워드】 antiviral immunity, mechanism, labeling, reveal,