Table 1 Functions of SARS-CoV-2 Non-structural proteins
Protein | Functions during viral infection |
|---|---|
NSP1 | Promote translation inhibition and cellular mRNA degradation [142, 143]. Block mRNA entry channel on the 40Â S ribosome [142, 143]. Prevent physiological conformation of the 48Â S preinitiation complex [142]. |
NSP2 | Potential role in viral pathogenesis by increasing viral ability of contagious [59]. Has a suggested role in calcium homeostasis and mitochondria biogenesis [147]. Vesicle trafficking [148]. |
NSP3 | Part of replicase–transcriptase complex in the infected cell [148] Contains papain-like protease (SCoV2-PLpro) activity that cleaves Nsp1, Nsp2 and Nsp3 from the viral polypeptide and regulates the virus-induced cytopathogenic effect and antiviral innate immunity [149,150,151]. Essential for replication and transcription of the viral genome [149, 152]. Nsp3 Mac1 domain binds to ADP-ribose (ADPr) and catalyzes the hydrolysis of ADPr-1′′ phosphate which is linked to SARS-CoV-2 associated cytokine storm and viral evasion of the innate immune response [153,154,155]. |
NSP4 | Potential role related to membrane rearrangement and formation of the double-membrane vesicles (DMVs) and viral replication [156, 157]. Has a suggested role in calcium homeostasis and mitochondria biogenesis [147]. |
NSP5 | 3Â C-like protease proteolytically cleaves viral polyprotein [148, 158]. Acts as epigenetic and gene-expression regulators [148]. |
NSP6 | Suppress IFN-I signaling [145]. Formation of autophagosome in the infected cell [159,160,161]. Vesicle trafficking [148]. Expected to involve in membrane rearrangement and formation of DMVs [159]. Interacts with the sigma receptor that has been linked to lipid remodeling and the stress response of the endoplasmic reticulum (ER) [148, 159]. |
NSP7 | Essential cofactor with NSP8 for NSP12 which are RNA polymerase [162,163,164,165]. Vesicle trafficking [148]. |
NSP8 | Essential cofactor with NSP7 for NSP12 which are RNA polymerase [162,163,164,165]. Involve in the regulation of lipid modification, RNA processing, epigenetic and gene expression [148]. |
NSP9 | RNA binding protein [166]. |
NSP10 | Form 2’-O-methyltransferase protein complex with NSP16 which catalyzes the methylation of viral RNA cap at the ribose 2′-O position [167, 168]. Vesicle trafficking [148]. |
NSP11 | Intrinsically disordered proteins contribute to the host cytosolic membrane affinity/interaction [169]. |
NSP12 | |
NSP13 | Helicase, 5′ triphosphatase that unwinds RNA helix and hydrolyzes NTPs [170,171,172,173]. Repress interferon production and signaling [174]. Acts as epigenetic and gene-expression regulators [148]. |
NSP14 | 3’-5’ exoribonuclease that is critical for proofreading and synthesis of viral RNA [175]. N-7 methyltransferase that involves in the capping of viral RNAs [175]. Repress interferon production and signaling [174]. |
NSP15 | Nidoviral RNA uridylate-specific endoribonuclease cleavage of RNA at the 3’-ends of uridylates to limit the accumulation of viral RNA and inhibit cellular sensing of the viral genome [176,177,178]. Vesicle trafficking [148]. Repress interferon production and signaling [174]. |
NSP16 | Form 2’-O-methyltransferase protein complex with NSP10 which catalyzes the methylation of viral RNA cap at the ribose 2′-O position [167, 168]. |