Table 2.

The structural proteins involved in immunopathology.

Name of the structural protein	Structure	Function on immunological aspects
		SARS-CoV-1	MERS	SARS-CoV-2
Nonstructural protein (Nsp)1 [[71], [72], [73]]	It is a leader protein, cleaved chain of ORF1b.	Antagonizes IFN-β production by decreasing the phosphorylation level of STAT1.	Helps in viral replication.	Detailed functions are still not known.
Nsp 15 [[74], [75], [76], [77], [78]]	Nidoviral RNA uridylate specific endoribonuclease (NendoU) that belongs to EndoU family. 34 KDa, around 345 amino acids, with three domains: N- terminal, middle and C-terminal domain.	Cleaves polyuridine (polyU) sequences from PUN RNAs and limits the formation of a PAMP and thus impedes the ability of activation the innate immune response to infection by MDA5.	Prevents activation of dsRNA sensors in host cell for evading immune system.	Inhibits the nuclear localization of IFR3 and antagonize the production of IFN and also target RNF41 (also known as NRDP1) to regulate innate immune system.
Nsp 9 and Nsp 10 [[78], [79], [80]]	The crystalline structure of Nsp9 of SARS-CoV revealed that the molecule forms two distinct types of dimers where the core of the protein is an open 6-stranded β-barrel that in turn comprises of two antiparallel β sheets packed orthogon.	Nsp10 regulates the activity of the 2′-O- Methyltransferase (2′-O- MTase) that prevents virus detection by cell innate immunity mechanisms and viral translation inhibition by the interferon-stimulated IFIT-1 protein.	According to available data Nsp9 helps in viral replication.	Interacts with NF-κB repressor, NKRF and activates IL-8/IL-6 mediated chemotaxis of neutrophils that results in inflammatory response in patients.
Nsp 13 [77,78,81]	It is a helicase of superfamily 1 and helps in viral RNA replication via unwinding of duplex RNA and DNA leaving a 5′ single-stranded tail in a 5′ to 3′ direction.	It acts as a helicase and helps in unfold the RNA-DNA hybrid.	Nsp13 attenuates the viral replication.	Targets TBK1 and TBKBP1 to inhibit interferon pathway to regulate innate immune response in host cell.
N (Nucleocapsid) protein [82]	N protein of SARS-CoV-2 is 29.9 kb in length, similar to 27.9 kb SARS-CoV and 30.1 kb MERS-CoV genome.	Generation of IFN is retarded upon crosstalk between the SPRY domain of TRIM25 and C terminus of the N protein as it blocks RIG-I ubiquitination by TRIM25.	Interacts with TRIM25 and interfere the IFN production in host cell.	Detailed functions are not clearly known.
ORF (open reading frame) 9b [83,84]	ORF-9b possesses a long hydrophobic lipid binding tunnel formed due to interwined dimer with an amphipathic outer surface	ORF-9b manipulates host cell mitochondrial function by disable MAVS signaling that results in reducing NLRP3 inflammasome activity, thus evading innate immune system.	Function in immune system is not known.	ORF9b in association with Tom70 interacts with a signaling adaptor MAVS indirectly
ORF6 [76,77]	SARS-CoV-1 and SARS-CoV-2 share only 69% amino acid similarity	It prevents primary production of interferon.	Helps in viral assembly and viral release and can act as a potential B cell epitope.	It prevents interferon production by various signaling molecules MDA5, MAVS, TBK1 and IRF3-5D, which is a phospho-mimic of the activated form of IRF3.
ORF3 [[85], [86], [87]]	Accessory protein formed by the cleavage of ORF1 and ORF1b.	ORF3a is responsible for activation of the NLRP3 inflammasome by secreting IL-1β.	Prevents interferon production and prevents inflammation.	The hypothesis is that ORF3a of SARS-CoV-2 may be less efficient in inflammasome activation.

IFIT, interferon-induced protein with tetratricopeptide repeats; IFN, interferon; IRF, interferon regulatory factor; MTase, methyltransferase; N, nucleocapsid; NendoU, nidoviral RNA uridylate specific endoribonuclease; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; NLRP3, NLR family pyrin domain containing 3; NRDP1, neuregulin receptor degradation protein 1; Nsps, non-structural proteins; ORFs, open reading frames; PAMP, pathogen associated molecular patterns; PolyU, poluuridine; RNF41, ring finger protein 41; SPRY, sprouty RTK signaling antagonist; STAT, signal transducer and activator of transcription; TBK1, TANK binding kinase 1; TBKBP1, TANK binding kinase-1, binding protein 1; TRIM25, tripartite motif containing 25.