Multiple SARS-CoV-2 proteins were identified to be involved in the suppression of interferon response. SARS-CoV-2 nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation. In addition, SARS-CoV-2 nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α2(KPNA2) to inhibit IRF3 nuclear translocation. Signal activator of transcription 1 (STAT1)/STAT2 phosphorylation and nuclear translocation were also blocked by ten viral proteins. It was shown that the inhibitory effect of nsp1 and nsp6 of SARS-CoV-2 for interferon signaling was more effective than those of SARS-CoV-1 and MERS-CoV.
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