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Table 4 Putative functions of SARS-CoV-2 proteins

From: Evolutionary trajectory of SARS-CoV-2 and emerging variants

Gene Protein Putative function References
Nsp1 Leader protein/host translation inhibitor Inhibits translation of host mRNAs and promotes expression of viral genes [320]
Nsp2 Non-structural protein 2 Modulates host cell survival signalling pathways [321]
Nsp3 Papain-like protease Proteolytic cleavage of polyprotein to generate Nsps 1–3, and inhibition of host IFN responses [322, 323]
Nsp4 Non-structural protein 4 Interacts with Nsp3 and host proteins to induce cytoplasmic autophagosomes for viral replication [324, 325]
Nsp5 Chymotrypsin-like protease Proteolytic cleavage of polyprotein to generate Nsps 4–16 and mediation of Nsp maturation [326, 327]
Nsp6 Non-structural protein 6 Interferes with delivery of viral factors to host lysosomes and inhibits IFN-1 responses [127, 128]
Nsp7 Primase complex Forms a complex with Nsp8 which interacts with RdRp (Nsp12) to transcribe viral genome [120]
Nsp8 Primase complex Forms a complex with Nsp7 which interacts with RdRp (Nsp12) to transcribe viral genome [120]
Nsp9 ssRNA-binding protein Binds to viral ssRNA and promotes replication [328]
Nsp10 Non-structural protein 10 Interacts with 3′–5′ exoribonuclease (Nsp14) and 2′ O-ribose methyltransferase (Nsp16) and promotes methylation of viral mRNA caps [328]
Nsp11 Non-structural protein 11 Released from cleavage of pp1a and forms N-terminal sequence of Nsp12 in pp1ab frameshift product. No known function [328]
Nsp12 RNA-dependent RNA polymerase (RdRp) Replicates and transcribes viral genome [326]
Nsp13 Helicase Unwinds dsRNA and dsDNA in viral replication [326, 329]
Nsp14 3′–5′ exoribonuclease/N7-guanine methyltransferase Proofreading during RNA replication (exoribonuclease) and viral mRNA capping (methyltransferase). Interacts with Nsp10 [330]
Nsp15 Nidoviral uridylate-specific endoribonuclease RNA processing and inhibition of host IFN responses [331]
Nsp16 2′ O-ribose methyltransferase Activated by Nsp10 for methylation of viral mRNA caps [332]
S Spike glycoprotein Cleaved into S1 and S2 subunits. S1 binds host receptor (ACE2) while S2 mediates viral and host membrane fusion [333]
ORF3a Orf3a viroporin Activates NF-kB and NLRP3 inflammasome to contribute to cytokine storm. Promotes viral release and may induce necrotic cell death [334,335,336]
ORF3b Accessory protein ORF3b IFN-1 antagonist [337]
E Envelope protein A viroporin involved in viral assembly, budding, and pathogenesis. Forms CoV envelope [338, 339]
M Membrane protein Forms viral membrane and induces N and S localization to the ER-Golgi-Intermediate compartment for virion assembly and budding [340]
ORF6 Accessory protein ORF6 IFN-1 antagonist [144]
ORF7a Accessory protein ORF7a SARS-CoV ortholog inhibits bone marrow stromal antigen 2 mediated tethering of virions to host plasma membrane [341]
ORF7b Accessory protein ORF7b SARS-CoV ortholog attenuates viral replication [342]
ORF8 Accessory protein ORF8 Inhibits IFN-1 activity and downregulates MHC-1 expression to evade host immunity [136, 137, 144]
N Nucleocapsid Involved in immune evasion through IFN-1 antagonism, nucleocapsid formation, viral RNA replication, and virion assembly [144, 145]
ORF9b Accessory protein ORF9b Suppresses IFN-1 responses through inhibition of TOM70 [343]
ORF9c Accessory protein ORF9c Interferes with IFN signalling, antigen presentation, and complement signalling. Induces IL-6 signalling [344]
ORF10 Accessory protein ORF10 Interacts with a Cullin 2 RING E3 ligase complex to potentially modulate ubiquitination [345]
  1. Findings are based on studies with SARS-CoV-2 proteins or SARS-CoV orthologs