Table 3.
Intra-viral interactions of SARS-CoV-2 proteins. All of the SARS-CoV-2 protein sequence identity and similarity percent are in comparison with SARS-CoV [68].
| SARS-CoV-2 protein | Approximate length (a.a.) | Seq. Identity (%) | Seq. Similarity (%) | Predicted function | Interaction(s) with other proteins | Self association | Reference(s) |
|---|---|---|---|---|---|---|---|
| Non-structural proteins | |||||||
| NSP 1 | 180 | 84.4 | 91.1 | A host shut-off factor blocks the ribosomal mRNA entry channel to inhibit host translation and antagonizes interferon induction | orf7b | - | [13] [69] [70] |
| NSP2 | 638 | 68.3 | 82.9 | Manipulate the host factors involved in calcium homeostasis at ER-mitochondrial sites. Controls the host milieu and cellular processes including mitochondria biogenesis. |
NSP15 NSP5 M orf10 orf7b |
+ | [52] [13] [71] [72] |
| NSP3 | 1945 | 76 | 91.8 | A papain-like protease (PLP) cleaves the viral polyprotein to produce NSP1-3. A multi-pass membrane protein that forms a complex with Nsp4 and Nsp6 necessary for viral replication. |
NSP4 NSP6 NSP2 |
- | [52] [73] [74] |
| NSP4 | 500 | 80 | 90.8 | A multi-span membrane protein that participates in organizing and localization of viral replication complex into double-membrane vesicles in the cytoplasm. | N orf3a orf7b NSP3 NSP6 |
- | [52] [13] [74] |
| NSP5 | 306 | 96.1 | 98.7 | A 3-chymotrypsin is like a protease (3CLpro) responsible for auto-proteolytic cleavage of ORF1a and ORF1b after the host ribosome translation. Also called the main protease (Mpro) because it releases and matures 13 NSPs (NSP4-NSP16). Predicted to cleave the human proteins and hijack innate immunity. Has a critical role in SARS-CoV-2 pathogenesis. |
NSP2 NSP13 M orf10 | + | [52] [13] [75] [76] [77] |
| NSP6 | 290 | 87.2 | 94.8 | A multi-pass membrane protein that ensures viral replication by inducing double-membrane vesicles for anchoring the replication complex. Suppresses IFN-I signaling and interferes with the function of autophagosomes in delivering virus fragments to lysosomes. |
NSP3 NSP4 | - | [52] [78] [74] [79] |
| NSP7 | 83 | 98.8 | 100 | Assembled into hexadecamer with NSP8 to form NSP7-NSP8-NSP12 core polymerase complex. NSP7-NSP8 serves as a primase for NSP12 polymerase activity. |
NSP12 NSP8 NSP9 orf7a orf7b |
+ | [52] [80] [13] [81] [82] |
| NSP8 | 198 | 97.5 | 99 | Assembled into hexadecamer with NSP7 to form NSP7-NSP8-NSP12 core polymerase complex. NSP7-NSP8 serves as a primase for NSP12 polymerase activity. |
NSP12 NSP7 NSP12 NSP13 M orf7b orf8 |
+ | [52] [13] [81] [80] |
| NSP9 | 113 | 97.3 | 98.2 | An ssRNA binding protein that plays a crucial role in viral replication through its dimer form. The substrate of the NSP12 NiRAN domain for NMPylation. |
Nsp8 Nsp12 NSP7 NSP16 orf7a orf10 |
+ | [52] [13] [83] [84] [85] |
| NSP10 | 139 | 97.1 | 99.3 | A cofactor of NSP14 and NSP16 that are necessary for cap formation and RNA 3′-end mismatch excision | NSP14NSP16 | - | [52] [13] [86] [87] |
| NSP11 | 13 | 84.6 | 92.3 | A disordered peptide whose function has not been recognized so far | - | - | [52] [88] |
| NSP12 | 932 | 96.4 | 98.3 | An RNA-dependent RNA polymerase (RdRp) that needs NSP7-NSP8 hexadecamer as a primase. | NSP8 NSP16 orf7a orf10 |
- | [52] [13] [81] [89] [80] |
| NSP13 | 601 | 99.8 | 100 | A Zinc binding helicase in replication-transcription complex. Act as a triphosphatase that initiates the first step in viral mRNA capping. Inhibits interferon activation and NF-κB promoter signaling. |
Nsp12 NSP5 NSP8 NSP16 orf7a orf10 |
- | [52] [13] [90] [70] |
| NSP14 | 527 | 95.1 | 98.7 | A bifunctional enzyme is necessary for the capping of viral mRNA via SAM-dependent methyltransferase domain and exonuclease activity for RNA mismatch repair. Needs NSP10 as a cofactor |
NSP10 orf6 NSP10 |
- | [52] [13] [86] [87] |
| NSP15 | 346 | 88.7 | 95.7 | A uridine-specific endoribonuclease (endoU) is essential for viral RNA synthesis. Potent interferon antagonist |
NSP2 NSP16 orf7a orf10 | - | [52] [13] [91] [92] |
| NSP16 | 298 | A cap-synthesizing enzyme. Its 2′O-methyltransferases activity is necessary for viral RNA integrity. Needs NSP10 as a cofactor. |
NSP9 NSP10 NSP12 NSP13 NSP15 M N orf3a orf7a orf10 |
- | [52] [13] [93] |
||
| Structural proteins | |||||||
| M (orf5) | 222 | 90.5 | 96.4 | The major protein in the envelope that play role in virus assembly and budding. Participates in viral entry and replication. Specifies the shape of the envelope and stabilizes the other structural proteins. |
NSP2 NSP5 NSP8 NSP16 M S N orf7a orf7b orf6 orf10 |
+ | [52] [13] [94] |
| S (orf2) | 1273 | 76.3 | 87 | Binds with the angiotensin-converting enzyme 2 (ACE2) receptor in the lung and mediates virus entry to the host cell. | M | + | [52] [13] |
| N (orf9a) | 419 | 90.5 | 94.3 | Packages the RNA genome into a helical ribonucleocapsid (RNP) structure. Protects SARS-CoV-2 RNA from recognition and degradation by host antiviral defense (RNAi). An interferon-1 antagonist |
NSP4 NSP16 E M orf7a orf10 |
+ | [52] [13] [95] |
| E (orf4) | 75 | 94.7 | 96.1 | A small multifunctional protein that plays a central role in virus assembly. Hijacks cell junction proteins in the lung and mediates host immune responses. |
E M N orf3a orf9b |
+ | [52] [13] [96] |
| Accessory factors | |||||||
| orf3a | 275 | 72.4 | 85.1 | A viroporin involve in virion release. A strong inducer of caspase-dependent apoptosis. |
NSP4 NSP16 E orf7a orf7b orf10 | + | [52] [13] [97] [98] |
| orf3b | 22(truncated form) | 7.1 | 9.5 | An interferon-1 antagonist and the modulator of host cell signaling pathways. | ? | ? | [52] [99] [100] |
| orf6 | 61 | 66.7 | 85.7 | The strongest interferon antagonist among all SARS-CoV-2 proteins. | NSP14 M orf6 orf7a | + | [52] [13] [92] |
| orf7a | 121 | 85.2 | 90.2 | An immunomodulator factor for human CD14+ monocytes. Interferon antagonist |
NSP7 NSP9 NSP12NSP13 NSP15 NSP16 M N orf3a orf6 |
+ | [52] [13] [101] [102] |
| orf7b | 43 | 85.4 | 97.2 | Interfering with cellular processes like heart rhythm and epithelial damaging using its leucine zipper motif. Common symptoms of covid-19 such as impaired heart rhythm, odor loss, and limitation of oxygen uptake may be related to this accessory factor. |
NSP1 NSP2 NSP4 NSP7 NSP8 M orf3a |
+ | [13] [103] |
| orf8 | 121 | 28.5 | 45.3 | Mediates escape from the immune system via their role in decreasing the expression of surface MHC-I. Responsible for spike production and localization in new virion surface. |
NSP8 | - | [52] [13] [104] [105] [106] |
| orf9b | 97 | 72.4 | 84.7 | Mediates escape from the immune system via their role in manipulating mitochondria membrane proteins. Antagonizes cytokines involved in pro-inflammatory response and limits IFN-β production |
E | + | [52] [13] [107] [108] |
| orf9c | 73 | 74.0 | 78.1 | A transmembrane protein that antagonizes interferon signaling and other antiviral immune responses. Regulates protein degradation in the endoplasmic reticulum. |
? | ? | [109] [110] |
| orf10 | 38 | Does not have a homolog in SARS-CoV | Not essential for SARS-CoV-2 pathogenicity in humans. | NSP2 NSP5 NSP8 NSP9 NSP12 NSP13 NSP15 NSP16 M N orf3a |
+ | [13] [111] [112] |
|