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SARS-CoV-2 Protein Interactome

Le SARS-CoV-2 est un bêta-coronavirus à ARN simple brin, enveloppé, à sens positif, appartenant à l'ordre des nidovirales. Au cours des trois premiers mois depuis son identification initiale en décembre 2019, le SARS-CoV-2 a causé plus de 800 000 cas confirmés et plus de 40 000 décès dans le monde du syndrome respiratoire aigu sévère associé COVID-19 (coronavirus disease 2019)1.

A l'heure actuelle, aucun vaccin n'est disponible pour freiner la propagation du virus. Une source potentielle pour la thérapeutique du COVID-19 sont les réactifs antiviraux existants qui sont soit déjà approuvés, soit en cours de développement pour le traitement des deux autres syndromes respiratoires - le SRAS et le MERS - causés par des coronavirus humains (hCoVs)2,3. Une compréhension plus approfondie de la fonction du virus et de ses protéines est essentielle pour l'application ciblée des médicaments existants et la découverte de nouveaux médicaments4,5,6.

Le génome de 30 kb du SARS-CoV-2 code 16 protéines non structurelles (Nsp1-16), quatre protéines structurelles (pic, enveloppe, nucléocapside, membrane) et neuf facteurs accessoires putatifs7. Nombre de ces protéines et polypeptides ont un certain nombre de partenaires d'interaction, en particulier dans les cellules pulmonaires, principal site d'infection du virus. Ces interactions avec la cellule hôte déterminent la capacité du virus à infecter la cellule, à reproduire son génome et à déclencher la production et la libération de nouvelles particules virales. En outre, plusieurs protéines du virus semblent avoir des partenaires d'interaction affectant les voies de l'immunité innée, telles que la voie de signalisation de l'interféron, la réponse inflammatoire NF-kappa B, la production d'interféron de type I et l'activation d'IRF-3.

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Au moins certains des membres du troisième groupe de protéines du SARS-CoV-2, les neuf facteurs accessoires (Orf3a-10), ont été impliqués dans la conduite de la progression du COVID-19. L'Orf3a induit l'apoptose et activerait le NF-kB et l'inflammasome NLRP3 impliqués dans la pyroptose, une forme hautement inflammatoire d'apoptose. Les antagonistes de l'interféron (IFN) de type I, Orf6 et Orf9b, inhibent la réponse IFN, les plus importantes cytokines antivirales innées.

Certaines de ces fonctions de régulation sont partagées avec d'autres virus humains pathogènes. Par conséquent, une compréhension plus approfondie de ces mécanismes peut conduire à l'identification de cibles et au développement de nouvelles thérapies pertinentes pour les futures pandémies virales.

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Protéines structurelles du SARS-CoV-2 : SARS-CoV-2 Spike Protein, SARS-CoV-2 Nucleocapsid Protein, SARS-CoV-2 S1 (RBD) Protein,

SARS-CoV-2 Protéines non structurelles: SARS-CoV-2 Protéines non structurelles

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Anticorps anti-SARS-CoV-2: anticorps anti-SARS-CoV-2

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Informations et produits complémentaires: Ressource CoV-2, Kits RT-PCR et qPCR SARS-CoV-2, SARS-CoV-2 ELISA Kits, SARS-CoV-2 Stades du cycle de vie et cibles d'inhibition.

References:

  • Dong, Ensheng; Du, Hongru; Gardner, L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect. Dis. (2020).
  • Morse, J. S., Lalonde, T., Xu, S. & Liu, W. R. Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV. Chembiochem 21, 730–738 (2020).
  • Li, G. & De Clercq, E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat. Rev. Drug Discov. 19, 149–150 (2020).
  • Báez-Santos, Y. M., St. John, S. E. & Mesecar, A. D. The SARS-coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds. Antiviral Res. 115, 21–38 (2015).
  • Kirchdoerfer, R. N. & Ward, A. B. Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat. Commun. 10, 2342 (2019).
  • Coutard, B. et al. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res. 176, 104742 (2020).
  • David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Matthew J. O’Meara, Jeffrey Z. Guo, Danielle L. Swaney, Tia A. Tummino, Ruth Huettenhain, Robyn M. Kaake, Alicia L. Richards, Beril Tutuncuoglu, Helene Foussard, Jyoti Batra, N. J. K. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug Repurposing. Nature. (2020).

CoV-2 Spike Protein

ZDHHC5 (Zinc Finger, DHHC-Type Containing 5):

CoV-2 Nucleocapsid Protein

RRP9 - Ribosomal RNA Processing 9, Small Subunit (SSU) Processome Component, Homolog (Yeast):

UPF1 - UPF1 Regulator of Nonsense Transcripts Homolog (Yeast):

MOV10 (Mov10, Moloney Leukemia Virus 10, Homolog (Mouse)):

G3BP2 (GTPase Activating Protein (SH3 Domain) Binding Protein 2):

PABPC4 - Poly(A) Binding Protein, Cytoplasmic 4 (Inducible Form):

G3BP1 - GTPase Activating Protein (SH3 Domain) Binding Protein 1:

LARP1 (La Ribonucleoprotein Domain Family, Member 1):

FAM98A (Family with Sequence Similarity 98, Member A):

PABPC1 - Poly(A) Binding Protein, Cytoplasmic 1:

DDX21 (DEAD (Asp-Glu-Ala-Asp) Box Polypeptide 21):

CoV-2 Envelope Protein

ZC3H18 (Zinc Finger CCCH-Type Containing 18):

Cwc27 (CWC27 Spliceosome-Associated Protein Homolog (S. Cerevisiae)):

SLC44A2 (Solute Carrier Family 44, Member 2):

AP3B1 (Adaptor-Related Protein Complex 3, beta 1 Subunit):

CoV-2 Membrane Protein

AASS - Aminoadipate Semialdehyde Synthase:

PSMD8 - Proteasome (Prosome, Macropain) 26S Subunit, Non-ATPase, 8:

PMPCB - Peptidase (Mitochondrial Processing) beta:

FAM8A1 - Family with Sequence Similarity 8, Member A1:

YIF1A - Yip1 Interacting Factor Homolog A (S. Cerevisiae):

TUBGCP2 (Tubulin, gamma Complex Associated Protein 2):

PMPCA - Peptidase (Mitochondrial Processing) alpha:

Slc25a21 - Solute Carrier Family 25 (Mitochondrial Oxodicarboxylate Carrier), Member 21:

TARS2 - threonyl-tRNA Synthetase 2, Mitochondrial (Putative):

FASTKD5 - FAST Kinase Domains 5:

C20orf4 - Chromosome 20 Open Reading Frame 4:

TUBGCP3 (Tubulin, gamma Complex Associated Protein 3):

SLC30A9 - Solute Carrier Family 30 (Zinc Transporter), Member 9:

BZW2 (Basic Leucine Zipper and W2 Domains 2):

ACADM - Acyl-CoA Dehydrogenase, C-4 To C-12 Straight Chain:

NSP1

NSP2

SLC27A2 - Solute Carrier Family 27 (Fatty Acid Transporter), Member 2:

EIF4E2 - Eukaryotic Translation Initiation Factor 4E Family Member 2:

FKBP15 (FK506 Binding Protein 15, 133kDa):

NSP4

TIMM10 (Translocase of Inner Mitochondrial Membrane 10 Homolog (Yeast)):

DNAJC11 (DnaJ (Hsp40) Homolog, Subfamily C, Member 11):

ALG11 - Asparagine-Linked Glycosylation 11, alpha-1,2-Mannosyltransferase Homolog (Yeast):

TIMM9 - Translocase of Inner Mitochondrial Membrane 9 Homolog (Yeast):

NSP5

NSP5_C145A

NSP6

ATP5L (ATP Synthase, H+ Transporting, Mitochondrial Fo Complex, Subunit G):

ATP13A3 (ATPase Type 13A3):

ATP6AP1 - ATPase, H+ Transporting, Lysosomal Accessory Protein 1:

NSP7

FAM162A - Family with Sequence Similarity 162, Member A:

NAT14 - N-Acetyltransferase 14 (GCN5-Related, Putative):

NDUFAF2 - NADH Dehydrogenase (Ubiquinone) 1 alpha Subcomplex, Assembly Factor 2:

QSOX2 (Quiescin Q6 Sulfhydryl Oxidase 2):

MOGS - Mannosyl-Oligosaccharide Glucosidase:

Acsl3 (Acyl-CoA Synthetase Long-Chain Family Member 3):

RAB2A - RAB2A, Member RAS Oncogene Family:

GNB1 (Guanine Nucleotide Binding Protein (G Protein), beta Polypeptide 1):

RAB18 (RAB18, Member RAS Oncogene Family):

NSP8

MRPS2 (Mitochondrial Ribosomal Protein S2):

NOL10 (Nucleolar Protein 10):

MPHOSPH10 - M-Phase phosphoprotein 10 (U3 Small Nucleolar Ribonucleoprotein):

SEPSECS (Sep (O-phosphoserine) tRNA:Sec (Selenocysteine) tRNA Synthase):

MRPS5 (Mitochondrial Ribosomal Protein S5):

NARS2 - Asparaginyl-tRNA Synthetase 2, Mitochondrial (Putative):

MRPS27 - Mitochondrial Ribosomal Protein S27:

SRP19 (Signal Recognition Particle 19kDa):

SRP54 (Signal Recognition Particle 54kDa):

SRP72 (Signal Recognition Particle 72kDa):

WHSC1 (Wolf-Hirschhorn Syndrome Candidate 1):

NSP9

SPG20 (Spastic Paraplegia 20 (Troyer Syndrome)):

DCAF7 (DDB1 and CUL4 Associated Factor 7):

GTF2F2 - General Transcription Factor IIF, Polypeptide 2, 30kDa:

MIB1 - Mindbomb E3 Ubiquitin Protein Ligase 1:

EIF4H (Eukaryotic Translation Initiation Factor 4H):

NSP10

ERGIC1 - Endoplasmic Reticulum-Golgi Intermediate Compartment (ERGIC) 1:

AP2A2 (Adaptor-Related Protein Complex 2, alpha 2 Subunit):

NSP11

Nsp12

LARP4B (La Ribonucleoprotein Domain Family, Member 4B):

SLU7 (SLU7 Splicing Factor Homolog (S. Cerevisiae)):

USP54 (Ubiquitin Specific Peptidase 54):

MYCBP2 (MYC Binding Protein 2):

RIPK1 (Receptor (TNFRSF)-Interacting serine-threonine Kinase 1):

PLEKHA5 (Pleckstrin Homology Domain Containing, Family A Member 5):

PRRC2B (Proline-Rich Coiled-Coil 2B):

PPIL3 - Peptidylprolyl Isomerase (Cyclophilin)-Like 3:

ZC3H7A (Zinc Finger CCCH-Type Containing 7A):

UBAP2L (Ubiquitin Associated Protein 2-Like):

AKAP8 (A Kinase (PRKA) Anchor Protein 8):

Znf318 - Zinc Finger Protein 318:

NSP13

CLIP4 (CAP-GLY Domain Containing Linker Protein Family, Member 4):

C1ORF50 (Chromosome 1 Open Reading Frame 50):

NINL (Ninein-Like):

PDE4DIP (phosphodiesterase 4D Interacting Protein):

TLE1 (Transducin-Like Enhancer of Split 1 (E(sp1) Homolog, Drosophila)):

TLE3 (Transducin-Like Enhancer of Split 3 (E(sp1) Homolog, Drosophila)):

JAKMIP1 (Janus Kinase and Microtubule Interacting Protein 1):

USP13 (Ubiquitin Specific Peptidase 13 (Isopeptidase T-3)):

GCC2 - GRIP and Coiled-Coil Domain Containing 2:

CIT (Citron (Rho-Interacting, serine/threonine Kinase 21)):

CCDC46 - Coiled-Coil Domain Containing 46:

PRKAR2B (Protein Kinase, CAMP-Dependent, Regulatory, Type II, beta):

PRKAR2A - Protein Kinase, CAMP-Dependent, Regulatory, Type II, alpha:

CEP250 (Centrosomal Protein 250kDa):

NIN - Ninein (GSK3B Interacting Protein):

AKAP9 (A Kinase (PRKA) Anchor Protein (Yotiao) 9):

GORASP1 - Golgi Reassembly Stacking Protein 1, 65kDa:

CEP350 (Centrosomal Protein 350kDa):

CDK5RAP2 (CDK5 Regulatory Subunit Associated Protein 2):

NSP14

NSP15

ORF3b

ORF3a

VPS39 (Vacuolar Protein Sorting 39 Homolog (S. Cerevisiae)):

VPS11 - Vacuolar Protein Sorting 11 Homolog (S. Cerevisiae):

SUN2 (Sad1 and UNC84 Domain Containing 2):

ALG5 (Asparagine-Linked Glycosylation 5, Dolichyl-Phosphate beta-Glucosyltransferase Homolog (S. Cerevisiae)):

ORF6

ORF7a

HEATR3 (HEAT Repeat Containing 3):

MDN1 - MDN1, Midasin Homolog (Yeast):

ORF8

CISD3 (CDGSH Iron Sulfur Domain 3):

KDELC2 (KDEL (Lys-Asp-Glu-Leu) Containing 2):

FOXRED2 - FAD-Dependent Oxidoreductase Domain Containing 2:

TOR1A - Torsin Family 1, Member A (Torsin A):

GGH (gamma-Glutamyl Hydrolase (Conjugase, Folylpolygammaglutamyl Hydrolase)):

OS9 (Osteosarcoma Amplified 9, Endoplasmic Reticulum Lectin):

EDEM3 (ER Degradation Enhancer, Mannosidase alpha-Like 3):

UGT2 - UDP-Glucose Glycoprotein Glucosyltransferase 2:

ADAMTS1 (ADAM Metallopeptidase with Thrombospondin Type 1 Motif, 1):

ERP44 - Endoplasmic Reticulum Protein 44:

CHPF (Chondroitin Polymerizing Factor):

PLEKHF2 - Pleckstrin Homology Domain Containing, Family F (With FYVE Domain) Member 2:

PCSK6 (Proprotein Convertase Subtilisin/kexin Type 6):

FKBP10 - FK506 Binding Protein 10, 65 KDa:

SIL1 (SIL1 Homolog, Endoplasmic Reticulum Chaperone (S. Cerevisiae)):

ORF9b

ORF9c

PIGS - Phosphatidylinositol Glycan Anchor Biosynthesis, Class S:

TAPT1 (Transmembrane Anterior Posterior Transformation 1):

TMED5 (Transmembrane Emp24 Protein Transport Domain Containing 5):

NLRX1 (NLR Family Member X1):

NDUFB9 - NADH Dehydrogenase (Ubiquinone) 1 beta Subcomplex, 9, 22kDa:

FAM134C (Family with Sequence Similarity 134, Member C):

ACAD9 - Acyl-CoA Dehydrogenase Family, Member 9:

ALG8 (Asparagine-Linked Glycosylation 8, alpha-1,3-Glucosyltransferase Homolog (S. Cerevisiae)):

NDUFAF1 - NADH Dehydrogenase (Ubiquinone) 1 alpha Subcomplex, Assembly Factor 1:

DPY19L1 (Dpy-19-Like 1 (C. Elegans)):

ABCC1 (ATP-Binding Cassette, Sub-Family C (CFTR/MRP), Member 1):

PIGO (Phosphatidylinositol Glycan Anchor Biosynthesis, Class O):

NDFIP2 (Nedd4 Family Interacting Protein 2):

ORF10

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