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SARS-CoV-2 Protein Interaktom

SARS-CoV-2 ist ein umhülltes, positiv-strangorientiertes, einzelsträngiges RNA beta Coronavirus, das zur Ordnung der Nidovirales gehört. In den ersten drei Monaten seit seiner erstmaligen Identifizierung im Dezember 2019 hat SARS-CoV-2 weltweit mehr als 800.000 bestätigte Fälle und über 40.000 Todesfälle des damit verbundenen schweren akuten respiratorischen Syndroms COVID-19 (Coronavirus-Krankheit 2019)1 verursacht.

Gegenwärtig ist kein Impfstoff verfügbar, um die Ausbreitung des Virus einzudämmen. Eine mögliche Quelle für COVID-19-Therapeutika sind bestehende antivirale Reagenzien, die entweder bereits für die Behandlung der beiden anderen Atemwegssyndrome - SARS und MERS -, die durch humane Coronaviren (hCoVs)2,3 verursacht werden, zugelassen sind oder sich in der Entwicklung befinden. Ein tieferes Verständnis der Funktion des Virus und seiner Proteine ist essentiell für den gezielten Einsatz bestehender und die Entdeckung neuer Medikamente4,5,6.

Das 30kb große SARS-CoV-2-Genom kodiert für 16 nicht-strukturelle Proteine (Nsp1-16), vier Strukturproteine (Spike, Hülle, Nukleokapsid, Membran) und neun putative akzessorische Faktoren7. Viele dieser Proteine und Polypeptide haben eine Reihe von Interaktionspartnern, insbesondere in Lungenzellen, dem primären Infektionsort des Virus. Diese Interaktionen mit der Wirtszelle bestimmen die Fähigkeit des Virus, die Zelle zu infizieren, sein Genom zu reproduzieren und die Produktion und Freisetzung neuer Viruspartikel auszulösen. Darüber hinaus scheinen mehrere Virusproteine Interaktionspartner zu haben, die angeborene Immunwege wie den Interferon-Signalweg, die NF-kappa-B-Entzündungsreaktion, die Typ-I-Interferon-Produktion und die IRF-3-Aktivierung beeinflussen.

Mindestens einige der Mitglieder der dritten Gruppe von SARS-CoV-2-Proteinen, die neun akzessorischen Faktoren (Orf3a-10), wurden mit der Progression von COVID-19 in Verbindung gebracht. Orf3a induziert Apoptose und aktiviert vermutlich NF-kB und das NLRP3-Inflammasom, das an der Pyroptose, einer stark entzündlichen Form der Apoptose, beteiligt ist. Die Typ-I-Interferon (IFN)-Antagonisten Orf6 und Orf9b hemmen die IFN-Antwort, die wichtigsten angeborenen antiviralen Zytokine.

Einige dieser regulatorischen Funktionen werden mit anderen humanpathogenen Viren geteilt. Daher könnte ein tieferes Verständnis dieser Mechanismen zur Identifizierung von Targets und zur Entwicklung neuer Therapeutika führen, die für zukünftige Viruspandemien relevant sind.

SARS-CoV-2 Strukturproteine: SARS-CoV-2 Spike Protein, SARS-CoV-2 Nucleocapsid Protein, SARS-CoV-2 S1 (RBD) Protein,

SARS-CoV-2 Non-Structural Proteins: SARS-CoV-2 Non-Structural Proteins

SARS-CoV-2 Antikörper: anti-SARS-CoV-2 Antikörper

Weitere Informationen und Produkte: CoV-2 Resource, SARS-CoV-2 RT-PCR und qPCR Kits, SARS-CoV-2 ELISA Kits, SARS-CoV-2 Lebenszyklusstadien & Inhibitionstargets

Referenzen:

  • 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

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

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):

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):

Znf318 - Zinc Finger Protein 318:

NSP13

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

C1ORF50 (Chromosome 1 Open Reading Frame 50):

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)):

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:

CHPF (Chondroitin Polymerizing Factor):

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

PCSK6 (Proprotein Convertase Subtilisin/kexin Type 6):

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)):

PIGO (Phosphatidylinositol Glycan Anchor Biosynthesis, Class O):

NDFIP2 (Nedd4 Family Interacting Protein 2):

ORF10

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