TABLE 2.
Evasion IFN-I system by HP-hCoV-encoded proteins.
| Protein | Virus | Mechanism | References |
| Non-structural proteins | |||
| NSP1 | HP-hCoVs | Suppressing phosphorylation of STAT1 and STAT2 | Xia et al., 2020; Kumar et al., 2021 |
| NSP3 | SARS-CoV-2 | Cleaving IRF3 directly | Moustaqil et al., 2021 |
| SARS-CoV-2, SARS-CoV, |
Cleaving ubiquitin-like protein ISG15 | Shin et al., 2020 | |
| HP-hCoVs | Exhibiting DUB and deISGylating activities | Ratia et al., 2014; Yang et al., 2014; Shin et al., 2020 | |
| SARS-CoV | Binding to IRF3 and inhibiting the degradation of IκBα | Devaraj et al., 2007; Frieman et al., 2009 | |
| MERS-CoV | Blocking IRF3 phosphorylation and nuclear transport | Yang et al., 2014 | |
| NSP5 | SARS-CoV-2, SARS-CoV |
Preventing nuclear translocation of phosphorylated IRF3 | Fung et al., 2021 |
| NSP6 | SARS-CoV-2, MERS-CoV |
Binding to TBK1 and suppressing IRF3 phosphorylation | Xia et al., 2020 |
| NSP8 | SARS-CoV-2 | Binding to MDA5 and impairing its K63-linked polyubiquitination | Yang et al., 2020 |
| NSP13 | SARS-CoV-2 | Binding and blocking TBK1 phosphorylation | Yuen et al., 2020 |
| NSP14 | SARS-CoV-2 | Inducing lysosomal degradation of the IFNAR1 (IFN-I receptor) and inhibiting STAT activation | Hayn et al., 2021 |
| Accessory proteins | |||
| ORF3a | SARS-CoV-2 | Impeding the phosphorylation of STAT1 | Lei et al., 2020; Xia et al., 2020 |
| SARS-CoV | Degradation of IFNAR1 | Minakshi et al., 2009 | |
| ORF3b | SARS-CoV-2, SARS-CoV |
Hampering the nuclear translocation of IRF3 | Konno et al., 2020 |
| ORF6 | SARS-CoV-2, SARS-CoV |
Binding directly to the Nup98 and Rae1 to Prevent bidirectional nucleocytoplasmic transport | Kopecky-Bromberg et al., 2007; Addetia et al., 2021 |
| SARS-CoV | Tethering KPNA2 and suppressing nuclear translocation of STAT1 | Frieman et al., 2007 | |
| ORF7a | SARS-CoV-2 | Impeding phosphorylation of STAT1 but STAT2 | Xia et al., 2020; Suryawanshi et al., 2021 |
| ORF7b | SARS-CoV-2 | Suppressing phosphorylation of STAT1 and STAT2 | Xia et al., 2020; Suryawanshi et al., 2021 |
| ORF8 | SARS-CoV-2 | Attenuating SeV induced IFN-β promoter activation and IFN-β mRNA level | Li et al., 2020a |
| ORF9b | SARS-CoV-2 | Interrupting K63-linked ubiquitination of NEMO | Wu J. et al., 2021 |
| SARS-CoV-2, SARS-CoV |
Interacting with human TOM70 | Jiang et al., 2020; Thorne et al., 2021 | |
| SARS-CoV | Targeting MAVS by usurping poly(C)-binding protein 2 (PCBP2) and the HECT domain E3 ligase AIP4 | Shi et al., 2014 | |
| ORF4a | MERS-CoV | Binding to PACT | Siu et al., 2014 |
| ORF4b | MERS-CoV | Interacting with TBK1 and IKKε, | Yang et al., 2015 |
| Associating with KPNA4 and suppressing nuclear translocation of NF-κB | Canton et al., 2018 | ||
| Structural proteins | |||
| M | SARS-CoV-2 | Interacting with MAVS | Fu et al., 2021 |
| Associating with MDA5, TRAF3, IKKℰ, and TBK1 and degrading TBK1 via the ubiquitin pathway | Sui et al., 2021 | ||
| SARS-CoV | Associating with RIG-I, TBK1, IKKε, and TRAF3 and impedes the formation of TRAF3/TANK/TBK1 complex | Siu et al., 2009 | |
| MERS-CoV | Interacting with TRAF3 | Lui et al., 2016 | |
| N | SARS-CoV-2 | Interacting with MDA5 and RIG-I and blocking the IRF3 phosphorylation and nuclear translocation | Chen et al., 2020 |
| SARS-CoV-2 | Blocking the STAT1 and STAT2 phosphorylation and nuclear translocation | Mu et al., 2020 | |
| SARS-CoV-2 | Inhibiting Lys63-linked poly-ubiquitination and aggregation of MAVS | Wang S. et al., 2021 | |
| HP-hCoVs | Interfering with TRIM25-mediated RIG-I ubiquitination | Hu et al., 2017; Chang et al., 2020; Gori Savellini et al., 2021 | |
| SARS-CoV | Binding with PACT | Ding et al., 2017 | |