The coronavirus disease 2019 (COVID-19) is determined by SARS-CoV-2 replication and host immune response, but studies evaluating viral evasion of immune response are lacking. Here we employed unbiased screening to identify SARS-CoV-2 proteins that antagonize type-I interferon (IFN-I) response. Three proteins were found to antagonize IFN-I production via distinct mechanisms: nsp6 binds TBK1 to suppress IRF3 phosphorylation; nsp13 binds and blocks TBK1 phosphorylation; and ORF6 binds importin KPNA2 to inhibit IRF3 nuclear translocation. Two sets of viral proteins were identified to antagonize IFN-I signaling through blocking STAT1/STAT2 phosphorylation or nuclear translocation. Remarkably, SARS-CoV-2 nsp1 and nsp6 suppressed IFN-I signaling more efficiently than SARS-CoV and MERS-CoV. Thus, when treated with IFN-I, a SARS-CoV2 replicon replicated to a higher level than chimeric replicons containing nsp1 or nsp6 from SARS-CoV or MERS-CoV. Altogether, the study has provided insights on SARS-CoV-2 evasion of IFN-I response and its potential impact on viral transmission and pathogenesis.

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Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that can cause human respiratory disease. The development of a detection method for this virus that can lead to rapid and accurate diagnosis would be significant. In this study, we established a nucleic acid visualization technique that combines the reverse transcription loop-mediated isothermal amplification technique and a vertical flow visualization strip (RT-LAMP-VF) to detect the N gene of MERS-CoV. The RT-LAMP-VF assay was performed in a constant temperature water bath for 30 min, and the result was visible by the naked eye within 5 min. The RT-LAMP-VF assay was capable of detecting 2 × 101 copies/μl of synthesized RNA transcript and 1 × 101 copies/μl of MERS-CoV RNA. The method exhibits no cross-reactivities with multiple CoVs including SARS-related (SARSr)-CoV, HKU4, HKU1, OC43 and 229E, and thus exhibits high specificity. Compared to the real-time RT-PCR (rRT-PCR) method recommended by the World Health Organization (WHO), the RT-LAMP-VF assay is easy to handle, does not require expensive equipment and can rapidly complete detection within 35 min.