Table 1.
Brief description of various structural, non-structural, and accessory proteins of SARS-CoV-2.
| Protein name | Length (aa) | Function | Binding site/ catalytic residues | Different domain and motifs | Drug binding sites | Ref. |
|---|---|---|---|---|---|---|
| S (Spike) | 1273 | Mediates binding to ACE2 | K417, E484, N487, F486, N501 | NTD (14–306), RBD (331–528), CTD1 (529–591), CTD2 (592–686), HR1 (910–985), HR2 (1163–1211), TM (1212–1234), CT (1235–1273) |
CTD of S1: V382 L390, C391, T393, T430, L517, A520, A522, L527, N544, L546, N564, F565, F782, A1056 S2 Domain: I870, D867, A1056, P1057, G1059, H1058, S730, M 730 M731, Y733, V860, L861, P863 |
(Chowdhury et al., 2020, Zhang et al., 2021) |
| E (Envelope) | 75 | Involved in virus morphogenesis and assembly | E8, N15, L18, L21, V25, L28, A32, T35 | NTD (1–8), TM (9–38), CTD (39–75) |
T9, G10, T11, I13, A36, L37, S16, N15, I33, E8, N15 | (Bhowmik et al., 2020, Mandala et al., 2020) |
| M (Membrane) | 222 | Important for the budding process of coronaviruses | NTD (1–19), Triple-TM (20–100), CTD (101–222), Motifaromatic-XX-aromatic motif (91-WXXY-94), Di-leucine motif (219-LL-220) |
Y50, L51, L54, L93, A98 | (Bhowmik et al., 2020, Yan et al., 2022) | |
| N (Nucleocapsid) | 419 | Promotes genome packaging, RNA chaperoning, intracellular protein transport, DNA degradation, interference in host translation |
A50, T57, H59, R89, R92, I94, S105, R107, R149, Y172 |
NTD (1–50), RBD (51–174), Linker (175–246), Dimerization domain (247–365), CTD (366–419) |
N48, N49, T50, A51, R89, Y112, Y110 | (Bhowmik et al., 2020, Cubuk et al., 2021, Khan et al., 2021b) |
| NSP1 | 180 | Recommended as leader protein which inhibit host translation and degrade host mRNAs | P153-N160, S166-N178 |
NTD (1–128), CTD (148–180), Motif KH (164–165) |
V35, E36, L39, V89, Y97, F143, F157, Q158 | (Schubert et al., 2020, Singh et al., 2021) |
| NSP2 | 638 | Binds to prohibitin 1 (PHB1) and 2 (PHB2) | V126, A127, C132, V157, L169, C240, Y242, W243, T256, G257 |
NTD (1–345), CTD (438–638) | P15, D16, N94, V96, A227 | (Ma et al., 2021, Maiti et al., 2020) |
| NSP3 (PLpro) | 1945 | Responsible for cleaving of NSP1, NSP2, and NSP3 from the N-terminal region of pp1a and 1ab | C111, H272, D286 | UbI1 (1–108), HVR (109–206), Mac1 or X (207–386), SUD (387–745), UbI2 (746–805), PLPro (806–1058), NBD (1059–1200), MD (1201–1340), TM (1341–1567), Y domain (1568–1945) |
L162, G163, D164, E167, P247, P248, Y264, Y268, Q269, Y273 | (Fu et al., 2021, Osipiuk et al., 2021, Yan et al., 2022) |
| NSP4 | 500 | Potential transmembrane scaffold protein which helps modify ER membranes | NA | TM1 (10–30), TM2 (280–300). TM3 (305–330), TM4 (355–380), CTD (381–500) |
NA | (Santerre et al., 2021, Yan et al., 2022) |
| NSP5 (3CLpro) | 306 | Cleaves viral polyprotein | C145, H41 |
N-finger (1–9), Domain-I (10–99), Domain-II (100–182), Domain-III (198–303) |
T24, T25, T26, H41, F140, L141, N142, G143, C145, H163, E166, P168, H172, Q189, T190, A191, Q192 | (Jin et al., 2020, Khan et al., 2021b, Rahman et al., 2020) |
| NSP6 | 290 | Induction of autophagosomes from host ER (Cottam et al., 2014, Cottam et al., 2014) | NA | NA | NA | |
| NSP7 | 83 | Forms hexadecameric complex with nsp8 for viral replication and participate as a cofactor for nsp12 | S4, D5, K7, C8, H36, L40, N37, V33 S15, L14, V11, A30, W29, E23 | Replicase domain (1–83) | R21, K43, D44 | (Wilamowski et al., 2021) |
| NSP8 | 198 | Makes heterodimer with nsp7 and nsp12 | P183, Y149, V131, M129, P133, A125, K127, V130, P121, L122, A110, L128, N118, I119, T123, K79, L117, I106, N109, P116, V115, M94, D112, C114, D99, L95, N104, L91, V83, L98, F92, A162, T84, R80, Q88, M90, I185, M87, A86 | Shaft domain (6–104), Head domain (105–196) |
A102, A150, R190, A194 | (Wilamowski et al., 2020) |
| NSP9 | 198 | RNA-binding protein which may participate in viral replication | N33, G100, M101, V102, L103, G104, S105 |
Single domain protein (1–109) Motif GxxxG (100–104) |
M12, S13, N33, T35, F40, L42, L94, N98 | (Khan et al., 2021b, Littler et al., 2021a) |
| NSP10 | 139 | Forms heterodimer complex with nsp14 and nsp16, acting as a cofactor for both and stimulates ExoN (viral exoribonuclease) and 2-O-methyltransferase activity | N3, V4, T5, F8, K9, D10, P20, T21, Q22, P24, T25, H26, L27, L38, C39, D41, F60, K61, M62, N63, Y64, V66, Y69, T127, N129, N130, T131, K196, K200, I201 | Single domain protein (1–139) | V21, D22, A26, G35, Q36, P37, I38, GLY52, Q65, R78, P107, V108 | (Halder, 2021, Lin et al., 2021) |
| NSP11 | 13 | Unknown | NA | NA | NA | NA |
| NSP12 (RdRp) | 932 | Replication and methylation | Y420, F415, F441, F440, F442, N552, A443, P412, G413, D445, Q444, T409, N447, R392, D390, L391, L389, N403, V405, L388, T402, L387, N386, A379, P323, L270, F396, F326, V398, L271, L514, P328, M666, V330, Y273, T324, T344, L329, P339, M380, R331, V338, K332, Y374, F340, A383, D336, S384, V341, S518, F407, L371, F368, D523, W509, S759, D760, D761 |
NiRAN (1–250), C-terminal RdRp (398–932), Motif G (499–511), Motif F (544–560), Motif A (612–626), Motif B (678–710), Motif C (753–767), Motif D (771–796), Motif E (810–820) |
M542, K545, S549, K551, R553, R555, V557, D618, C622, ASP623, S682, S759, D760, D761, R836 | (Ahmed et al., 2020, Khan et al., 2021b, Zhang et al., 2020c) |
| NSP13 (Helicase) | 596 | A helicase core domain participates in binding interaction with ATP. Zn-binding domain is involving in replication and transcription | R178, H230, N361, S468, T532, D534 | ZBD (1–100), SD (101–150), 1B domain (151–261), 1A domain (262–442), 2A domain (443–601) |
V45, Y70, F90, P283, G285, T286, G287, K288, H290, R443, E540 | (Chen et al., 2020, Malone et al., 2021, Yan et al., 2021) |
| NSP14 (ExoN) | 527 | Acting on both ssRNA and dsRNA in a 3′ to 5′ direction and a N7-guanine methyltransferase activity | D90, E92, E191, H268, D273 | Flanking region (1–50), ExoN (51–287), N7-MTase (288–527), DEDD motif |
W385, N386, Y420, F426, F506 |
(Devkota et al., 2021, Tahir, 2021) |
| NSP15 | 346 | Uridine-specific endoribonuclease activity | H235, H250, K290, T341, Y343, S294 |
N-domain (1–64), Middle domain (65–182), endoU (207–347) |
F44, E45, D92, H250, Y290, V292, C293, S294, Y343 | (Khan et al., 2021b, Kim et al., 2021) |
| NSP16 | 298 | RNA-cap methyltransferase |
K46, D130, K170, E203 | NTD (1–29), Mtase domain (30–210), CTD (211–298) |
A80, T83, A84, L86, T94, L95, L96, V97, D98, S99, D100 | (Rosas-Lemus et al., 2020, Vithani et al., 2021) |
| ORF3a | 275 | Infection, inducing apoptosis | NA | NTD (1–34) TM1 (35–56), TM2 (76–99), TM3 (103–125), CR domain (127–133), CTD (208–264), TRAF3-binding motif (36–40), CBM (141–149), Motif YXXΦ (160–163), Motif EXD (171–173) |
Y61, I62, I63, T64, I118, V121, R122, Y206 | (Kern et al., 2021) |
| ORF6 | 61 | Type 1 IFN antagonist | D53, E55, M58, E59, D61 | Interaction motif (56–61) | NA | (Gordon et al., 2020, Li et al., 2022) |
| ORF7a | 121 | Triggers an immune response in host cells | NA | Signal peptide (1–15), Ig-like ectodomain (16–96), TM region (97–116), ER retention motif (117–121) |
E33, C35, S36, S37, T39, Y40, E41, G42, S44, P45, F46, P48, F65 | (Gorgulla et al., 2021) |
| ORF8 | 121 | Disrupts IFN-I signaling when exogenously overexpressed in cells | P85, F86, T87, I88, N89, C90, Q91, E92 | D1 domain (1–15), D2 domain (16–121), Catalytic core motif (85–92) |
I47-L60, V62, D63, Y73–I76, Y79, T80, Q91, K94, L95 | (Cavasotto et al., 2021, Hassan et al., 2021) |
NTD = N-terminal Domain, RBD = Receptor Binding Domain, CTD = C-terminal Domain, TM = Transmembrane Domain, UbI1 = ubiquitin-like domain 1, SUD = SARS-unique domain, HVR = hypervariable region, PL2pro = papain-like protease, MD = Marker domain, NBD = nucleic acid-binding domain, ZBD = zinc-binding domain, SD = stalk domain.