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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