SARS-CoV-2 virus proteins

From Proteopedia

SARS-CoV-2 Protein Organization, from Gordon et al. & Krogan (2020)^[1] )

Organization of SARS-CoV-2 virus (from Holmes & Enjuanes (2003)^[2])

Background

The genome of the SARS-CoV-2 virus codes for 28 proteins: Out of those, 19 have already been characterized structurally. For the rest there are accurate AlphaFold2 predicted structures.
Details of the 3D structure & function of the key proteins & RNA inside the virus can be seen in the NY Times^[3]. "The first viral protein created inside the infected cell, ORF1ab, is actually a chain of 16 proteins joined together. Two of these proteins act like scissors, snipping the links between the different proteins and freeing them to do their jobs."^[3]

SARS-CoV-2 Proteins

• NSP1: Inhibits host translation by interacting with the 40S ribosomal subunit.
• NSP2: May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2.
• NSP3: Papain-like proteinase
• NSP4: Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[1][2]
• NSP5: Main protease, which is a cysteine protease that is essential for the viral life cycle.
• NSP6: AlphaFold2 Theoretical Model - Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic.
• NSP7: together with NSP8, aid the virus to make new copies of the RNA genome.
• NSP8: together with NSP7, aid the virus to make new copies of the RNA genome.
• NSP9: binds to RNA & DNA but preferably to ssRNA and may interact with the replication complex (consisting of nsp7, nsp8 and nsp12).
• NSP10: or replicase polyprotein 1ab plays a pivotal role in SARS-CoV viral transcription by stimulating both NSP14 3'-5' exoribonuclease and NSP16 2'-O-methyltransferase activities and therefore plays an essential role in viral mRNAs cap methylation ^[4][5].
• NSP11: AlphaFold2 Theoretical Model - is the 13 amino acid peptide at the C-term of the large SARS-CoV-2 polyprotein ORF1ab (pp1a). Neither its functions, nor if it is expressed in vivo is clear.
• NSP12: RNA-directed RNA polymerase (RdRp)
• NSP13: Helicase (HEL), Multi-functional protein with a zinc-binding domain in N-terminus*
• NSP14: 3'-5' exoribonuclease
• NSP15: Uridylate-specific endoribonuclease (NendoU)
• NSP16: Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs (2'-O-MT)
• Protein S: Spike or Surface glycoprotein (S) and SARS-CoV-2 protein S priming by furin
• ORF3a: Forms homotetrameric potassium sensitive ion channels (viroporin) and may modulate virus release.
• Protein E: Plays a central role in virus morphogenesis and assembly.
• Protein M: AlphaFold2 Theoretical Model - Component of the viral envelope.
• ORF6: AlphaFold2 Theoretical Model : Could be a determinant of virus virulence.
• ORF7a: Non-structural protein which is dispensable for virus replication in cell culture.
• ORF8: Open Reading Frame 8.
• Protein N: AlphaFold2 Theoretical Model - Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP).
• ORF10‎:AlphaFold2 Theoretical Model - It is currently unclear whether this region translates into a functional protein.

See also

Coronavirus_Disease 2019 (COVID-19)
COVID-19 AlphaFold2 Models

References

1. ↑ Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Huttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu-Ozturk D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, Garcia-Sastre A, Shokat KM, Shoichet BK, Krogan NJ. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020 Jul;583(7816):459-468. doi: 10.1038/s41586-020-2286-9. Epub 2020 Apr, 30. PMID:32353859 doi:http://dx.doi.org/10.1038/s41586-020-2286-9
2. ↑ Holmes KV, Enjuanes L. Virology. The SARS coronavirus: a postgenomic era. Science. 2003 May 30;300(5624):1377-8. doi: 10.1126/science.1086418. PMID:12775826 doi:http://dx.doi.org/10.1126/science.1086418
3. ↑ ^{3.0 3.1} NY Times (3-Apr-2020) Bad News Wrapped in Protein: Inside the Coronavirus Genome
4. ↑ Modeling of the SARS-COV-2 Genome
5. ↑ Zhang C, Zheng W, Huang X, Bell EW, Zhou X, Zhang Y. Protein Structure and Sequence Reanalysis of 2019-nCoV Genome Refutes Snakes as Its Intermediate Host and the Unique Similarity between Its Spike Protein Insertions and HIV-1. J Proteome Res. 2020 Apr 3;19(4):1351-1360. doi: 10.1021/acs.jproteome.0c00129., Epub 2020 Mar 24. PMID:32200634 doi:http://dx.doi.org/10.1021/acs.jproteome.0c00129