Table 2.
Summary of SARS-CoV-2 open reading frame proteins and their functions.
| Proteins | Length (AA) | Function (Ref) |
|---|---|---|
| ORF3a | 275 | Ion channel [25] Replication and virulence [26] Activating pro-IL-1β gene expression and IL-1β secretion [27] Ultimately activating NFκB signaling and NLRP3 inflammasomes [27] Promoting the cytokine storm [27] Necrotic cell death and lysosomal damage [28] |
| ORF3b | 22 | IFN antagonism [29] |
| ORF3c | 41 | Unknown [30] |
| ORF3d | 57 | Interaction with STOML2 [31] With ORF8, elicits the strongest antibody responses [32] |
| ORF6 | 61 | Localized to the ER, autophagosomes, and lysosomes [33] Blocks STAT transportation from the cytoplasm to the nucleus [34] IFN antagonist [34,35] Inhibits STAT1 nuclear transportation [36] Accumulation of hnRNPA1 in the nucleus [37] |
| ORF7a | 121 | Antagonizes the IFN-I response [38] Hijacks the host ubiquitin system to enhance and antagonize IFN-I responses [39] Decreases antigen-presenting ability and induces expression of pro-inflammatory cytokines [40] |
| ORF7b | 43 | Transmembrane protein localized in the Golgi [41] |
| ORF8 | 121 | Apoptosis [42] Antagonizing the IFN signaling pathway [43] Interacts with MHC-I [24] IFN I antagonist [44] Activates IL-17 signaling pathway and promote proinflammatory factors [45] |
| ORF9b | 97 | Induces autophagy in host cells mediated by ATG5 [46] Tom70 forms a complex with ORF9b to modulate the host immune response by compromising type I IFN synthesis [47] Activation of inflammasome [48] Promotes proteasomal degradation of Drp1 [46] |
| ORF9c | 73 | Protein interaction between ORF9c protein and NFκB-related molecules [31] Interactions with NFκB-related molecules [49] Interferes with IFN signaling [31,50,51] |
| ORF 10 | 38 | Unknown [52] |
ATG5, autophagy-related 5; Drp1, dynein-related protein 1; ER, endoplasmic reticulum; hnRNPA1, heterogeneous nuclear ribonucleoprotein A1; IFN, interferons; IL, interleukin; MHC, major histocompatibility complex; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; NLRP3, NLR family pyrin domain-containing 3; ORF, open reading frame; STAT1, signal transducer and activator of transcription 1; STOML2, stomatin-like 2.