Table.
Betacoronavirus genes, related proteins and their inhibitors
| Gene1) | Protein (domain) and size (a.a.) | Found in virion | Protein function | Viral protein inhibitor2) | Reference |
|---|---|---|---|---|---|
| 1ab3) | (7096) | – | – | – | – |
| nsp1 | (180) | – | degradation of cell mRNAs, suppressed IFN | – | – |
| nsp2 | transmembrane protein (638) | – | activated NFKβ, augmented inflammation | – | – |
| nsp3 | transmembrane protein PLpro4) (1945) | – | cysteine protease, downmodulated p53 and IFN induction | ritonavir/ lopinavir | [6-9] |
| nsp4 | (500) | – | DMV formation | – | – |
| nsp5 | Mpro (306) | – | cysteine protease, downmodulated IFN | ritonavir/lopinavir | [6-9] |
| nsp6 | (290) | – | restricted autophagy, DMV formation | – | – |
| nsp7 | (83) | – | cofactor nsp8, nsp12 | – | – |
| nsp8 | (198) | – | cofactor nsp7, nsp12 | – | – |
| nsp9 | (113) | – | dimerization and RNA binding | – | – |
| nsp10 | (139) | – | platform for nsp12, nsp14 | – | – |
| nsp11 | (13) | – | (?)5) | – | – |
| nsp12 | Pol (932) | – | RNA-dependent RNA polymerase | ribavirin | [10-12] |
| favipiravir | [13] | ||||
| remdesivir | [6, 14, 15] | ||||
| nsp13 | (601) | – | RNA helicase, 5′-phosphatase | – | – |
| nsp14 | (527) | – | 3′→5′ exoribonuclease | – | – |
| nsp15 | (346) | – | endoribonuclease, dsRNA sensor | – | – |
| nsp16 | (298) | – | 2-O-MTase, MDA5 sensor, IFN pathway inhibitor | – | – |
| S | envelope protein (spike protein) (1278) | + | virus entry into target cells | protease inhibitors | [16-22]6) |
| fusion-inhibiting peptides | [23]7) | ||||
| chloroquine | [24-26] | ||||
| antibodies | [27-32] | ||||
| 3a | (275) | (?)5) | augmented cytokine response and inflammation via NLRP3 | – | – |
| E | envelope protein (viroporin) (75) | + | ion channel, regulates virion assembly | chloroquine | [24-26] |
| antibodies | [27-32] | ||||
| M | viral matrix protein (222) | + | links viral envelope and nucleocapsid | – | – |
| 6 | (61) | (?) | – | – | – |
| 7a/b | transmembrane protein (121/43) | + | enhances viral yield | – | – |
| 8a | transmembrane protein (121) | (?) | ubiquitinates IRF3, lowers IFN production | – | – |
| 9b | (38) | (?) | – | – | – |
| N | nucleocapsid protein (419) | + | forms internal nucleocapsid together with viral RNA | – | – |
Comments.
1) Genes and relevant protein names (or domains) in virus SARS-CoV-2 listed in order starting from the 5′-end in genomic RNA [5]. GenBank data were used to determine the size of the protein (the number of amino acid residues) (ac.n. YP-009725301.1).
2) Classes of inhibitor agents with identified mode of action are shown.
3) Functions for proteins nsp1-nsp16 (proteolytic products derived from polyprotein 1ab) are considered elsewhere [5, 33, 34].
4) SARS-CoV-2 lacks in protein nsp3 one of two papain-like protease domains but preserves ubiquitin-like domains [35].
5) A question mark (?) denotes gene products with unidentified function (no data).
6) Protease inhibitors (camostat, aprotinin, lutevirin, etc.) indirectly suppress S protein-driven entry by inhibiting its proteolytic cleavage into active subunits S→S1/S2.
7) Fusion-inhibiting oligopeptides targeting S protein upon entry into host cells [23].