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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

TMPRSS2 (Transmembrane Protease, serine 2):

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

CoV-2 Nucleocapsid Protein

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

MOV10 (Moloney Leukemia Virus 10):

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):

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

RPL36 (Ribosomal Protein L36):

SNIP1 (Smad Nuclear Interacting Protein 1):

RBM28 (RNA Binding Motif Protein 28):

CSNK2A2 (Casein Kinase 2, alpha Prime Polypeptide):

CoV-2 Envelope Protein

ZC3H18 (Zinc Finger CCCH-Type Containing 18):

Cwc27 (CWC27 Spliceosome-Associated Protein Homolog):

SLC44A2 (Solute Carrier Family 44, Member 2):

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

BRD2 (Bromodomain Containing 2):

CoV-2 Membrane Protein

AASS (Aminoadipate Semialdehyde Synthase):

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

PMPCB (Peptidase (Mitochondrial Processing) beta):

GGCX (gamma-Glutamyl Carboxylase):

REEP5 (Receptor Accessory Protein 5):

INTS4 (Integrator Complex Subunit 4):

ATP1B1 (ATPase, Na+/K+ Transporting, beta 1 Polypeptide):

FAM8A1 (Family with Sequence Similarity 8, Member A1):

REEP6 (Receptor Accessory Protein 6):

YIF1A (Yip1 Interacting Factor Homolog A):

TUBGCP2 (Tubulin, gamma Complex Associated Protein 2):

PITRM1 (Pitrilysin Metallopeptidase 1):

PMPCA (Peptidase (Mitochondrial Processing) alpha):

TARS2 (threonyl-tRNA Synthetase 2, Mitochondrial):

FASTKD5 (FAST Kinase Domains 5):

ETFA (Electron-Transfer-Flavoprotein, alpha Polypeptide):

C20orf4 (Chromosome 20 Open Reading Frame 4):

TUBGCP3 (Tubulin, gamma Complex Associated Protein 3):

ATP6V1A (ATPase, H+ Transporting, Lysosomal 70kDa, V1 Subunit A):

AKAP8L (A Kinase (PRKA) Anchor Protein 8-Like):

SLC30A7 (Solute Carrier Family 30 (Zinc Transporter), Member 7):

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

BZW2 (Basic Leucine Zipper and W2 Domains 2):

ADCK4 (AarF Domain Containing Kinase 4):

NSP1

POLA2 (Polymerase (DNA Directed), alpha 2 (70kD Subunit)):

POLA1 (DNA Polymerase alpha):

PRIM2 (Primase, DNA, Polypeptide 2 (58kDa)):

PRIM1 (Primase, DNA, Polypeptide 1 (49kDa)):

GLT25D1 (Glycosyltransferase 25 Domain Containing 1):

NSP2

KIAA1033 (KIAA1033):

RAP1GDS1 (RAP1, GTP-GDP Dissociation Stimulator 1):

GIGYF2 (GRB10 Interacting GYF Protein 2):

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

EIF4E2 (Eukaryotic Translation Initiation Factor 4E Family Member 2):

POR (P450 (Cytochrome) Oxidoreductase):

FKBP15 (FK506 Binding Protein 15, 133kDa):

NSP4

TIMM10 (Translocase of Inner Mitochondrial Membrane 10):

C19ORF52 - TIMM29:

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)):

NUP210 (Nucleoporin 210kDa):

NSP5

NSP5_C145A

NSP6

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

SIGMAR1 (sigma Non-Opioid Intracellular Receptor 1):

ATP13A3 (ATPase Type 13A3):

ATP6AP1 (ATPase, H+ Transporting, Lysosomal Accessory Protein 1):

NSP7

RAB10 (RAB10, Member RAS Oncogene Family):

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

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

TOR1AIP1 (Torsin A Interacting Protein 1):

QSOX2 (Quiescin Q6 Sulfhydryl Oxidase 2):

GNG5 (G Protein gamma 5):

DCAKD (dephospho-CoA Kinase Domain Containing):

CYB5B (Cytochrome B5 Type B (Outer Mitochondrial Membrane)):

HS2ST1 (Heparan Sulfate 2-O-Sulfotransferase 1):

COMT (Catechol-O-Methyltransferase):

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

AGPS (Alkylglycerone Phosphate Synthase):

RAB2A (RAB2A, Member RAS Oncogene Family):

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

RHOA (Ras Homolog Gene Family, Member A):

RAB7A (RAB7A, Member RAS Oncogene Family):

Rab5c (RAB5C, Member RAS Oncogene Family):

RAB1A (RAB1A, Member RAS Oncogene Family):

RAB18 (RAB18, Member RAS Oncogene Family):

RAB14 (RAB14, Member RAS Oncogene Family):

RAB8A (RAB8A, Member RAS Oncogene Family):

MOSC1 (MOCO Sulphurase C-terminal Domain Containing 1):

DNAJC19 (DnaJ (Hsp40) Homolog, Subfamily C, Member 19):

SCARB1 (Scavenger Receptor Class B, Member 1):

NSP8

NGDN (Neuroguidin, EIF4E Binding Protein):

MRPS2 (Mitochondrial Ribosomal Protein S2):

NOL10 (Nucleolar Protein 10):

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

CCDC86 (Coiled-Coil Domain Containing 86):

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):

MRPS25 (Mitochondrial Ribosomal Protein S25):

DDX10 (DEAD (Asp-Glu-Ala-Asp) Box Polypeptide 10):

SRP19 (Signal Recognition Particle 19kDa):

SRP54 (Signal Recognition Particle 54kDa):

SRP72 (Signal Recognition Particle 72kDa):

EXOSC5 (Exosome Component 5):

WHSC1 (Wolf-Hirschhorn Syndrome Candidate 1):

MEPCE (Methylphosphate Capping Enzyme):

LARP7 (La Ribonucleoprotein Domain Family, Member 7):

HECTD1 (HECT Domain Containing 1):

EXOSC8 (Exosome Component 8):

EXOSC3 (Exosome Component 3):

AATF (Apoptosis Antagonizing Transcription Factor):

NSP9

SPG20 (Spastic Paraplegia 20 (Troyer Syndrome)):

NUP54 (Nucleoporin 54kDa):

NEK9 (NIMA (Never in Mitosis Gene A)- Related Kinase 9):

DCAF7 (DDB1 and CUL4 Associated Factor 7):

GTF2F2 (General Transcription Factor IIF, Polypeptide 2, 30kDa):

ZNF503 (Zinc Finger Protein 503):

NUP88 (Nucleoporin 88kDa):

MIB1 (Mindbomb E3 Ubiquitin Protein Ligase 1):

MAT2B (Methionine Adenosyltransferase II, beta):

EIF4H (Eukaryotic Translation Initiation Factor 4H):

NUP214 (Nucleoporin 214kDa):

NSP10

GRPEL1 (GrpE-Like 1, Mitochondrial):

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

GFER (Growth Factor, Augmenter of Liver Regeneration):

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

AP2M1 (Adaptor-Related Protein Complex 2, mu 1 Subunit):

NSP11

TBCA (Tubulin Folding Cofactor A):

Nsp12

SBNO1 (Strawberry Notch Homolog 1):

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

SLU7 (SLU7 Splicing Factor Homolog):

USP54 (Ubiquitin Specific Peptidase 54):

RBM41 (RNA Binding Motif Protein 41):

UBAP2 (Ubiquitin Associated Protein 2):

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):

TYSND1 (Trypsin Domain Containing 1):

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 - ZNF318:

TCF12 (Transcription Factor 12):

PDZD11 (PDZ Domain Containing 11):

CRTC3 (CREB Regulated Transcription Coactivator 3):

BCKDK (Branched Chain Ketoacid Dehydrogenase Kinase):

NSP13

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

C1ORF50 (Chromosome 1 Open Reading Frame 50):

NINL (Ninein-Like):

GCC1 (GRIP and Coiled-Coil Domain Containing 1):

PDE4DIP (phosphodiesterase 4D Interacting Protein):

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

TLE3 (Transducin-Like Enhancer Protein 3):

ERC1 (ELKS/RAB6-Interacting/CAST Family Member 1):

FYCO1 (FYVE and Coiled-Coil Domain Containing 1):

JAKMIP1 (Janus Kinase and Microtubule Interacting Protein 1):

MIPOL1 (Mirror-Image Polydactyly 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):

GOLGB1 - Golgin B1:

CEP250 (Centrosomal Protein 250kDa):

CEP135 (Centrosomal Protein 135kDa):

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

PKA (Protein Kinase A):

GORASP1 (Golgi Reassembly Stacking Protein 1, 65kDa):

GRIPAP1 (GRIP1 Associated Protein 1):

CEP350 (Centrosomal Protein 350kDa):

CENPF (Centromere Protein F):

CDK5RAP2 (CDK5 Regulatory Subunit Associated Protein 2):

AES (Amino-terminal Enhancer of Split):

HSBP1 (Heat Shock Factor Binding Protein 1):

NSP14

NSP15

NUTF2 (Nuclear Transport Factor 2):

RNF41 (Ring Finger Protein 41):

ORF3b

ORF3a

VPS39 (Vacuolar Protein Sorting 39 Homolog):

TRIM59 (Tripartite Motif Containing 59):

VPS11 (Vacuolar Protein Sorting 11 Homolog):

SUN2 (Sad1 and UNC84 Domain Containing 2):

HMOX1 (Heme Oxygenase (Decycling) 1):

ARL6IP6 (ADP-Ribosylation-Like Factor 6 Interacting Protein 6):

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

CLCC1 (Chloride Channel CLIC-Like 1):

ORF6

RAE1 (RAE1 RNA Export 1 Homolog (S. Pombe)):

ORF7a

HEATR3 (HEAT Repeat Containing 3):

MDN1 (MDN1, Midasin Homolog):

ORF8

CISD3 (CDGSH Iron Sulfur Domain 3):

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

KDELC1 (KDEL (Lys-Asp-Glu-Leu) Containing 1):

PUSL1 (Pseudouridylate Synthase-Like 1):

FOXRED2 (FAD-Dependent Oxidoreductase Domain Containing 2):

PLD3 (Phospholipase D family member 3):

TM2D3 (TM2 Domain Containing 3):

HS6ST2 (Heparan Sulfate 6-O-Sulfotransferase 2):

PLOD2 (Procollagen-Lysine 2-Oxoglutarate 5-Dioxygenase 2):

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

NPC2 (Niemann-Pick Disease, Type C2):

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

OS9 (Osteosarcoma Amplified 9, Endoplasmic Reticulum Lectin):

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

ADAM9 (ADAM Metallopeptidase Domain 9):

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

FBXL12 (F-Box and Leucine-Rich Repeat Protein 12):

DNMT1 (DNA (Cytosine-5)-Methyltransferase 1):

ERP44 (Endoplasmic Reticulum Protein 44):

CHPF (Chondroitin Polymerizing Factor):

NEU1 (Sialidase 1 (Lysosomal Sialidase)):

POFUT1 (Protein O-Fucosyltransferase 1):

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

PLAT (Plasminogen Activator, Tissue):

SMOC1 (SPARC Related Modular Calcium Binding 1):

SDF2 (Stromal Cell Derived Factor 2):

PCSK6 (Proprotein Convertase Subtilisin/kexin Type 6):

MFGE8 (Milk Fat Globule-EGF Factor 8 Protein):

GDF15 (Growth Differentiation Factor 15):

FKBP10 (FK506 Binding Protein 10, 65 KDa):

FKBP7 (FK506 Binding Protein 7):

SIL1 (Nucleotide Exchange Factor SIL1):

ORF9b

SLC9A3R1 (Solute Carrier Family 9, Subfamily A (NHE3, Cation Proton Antiporter 3), Member 3 Regulator 1):

CHMP2A (Charged Multivesicular Body Protein 2A):

MARK3 (MAP/microtubule Affinity-Regulating Kinase 3):

MARK2 (MAP/microtubule Affinity-Regulating Kinase 2):

MARK1 (MAP/microtubule Affinity-Regulating Kinase 1):

BAG5 (BCL2-Associated Athanogene 5):

PTBP2 (Polypyrimidine Tract Binding Protein 2):

CDSE1 (Cold Shock Domain Containing E1, RNA-Binding):

ORF9c

TMEM39B (Transmembrane Protein 39B):

PIGS (Phosphatidylinositol Glycan Anchor Biosynthesis, Class S):

TAPT1 (Transmembrane Anterior Posterior Transformation 1):

SLC30A6 (Solute Carrier Family 30 (Zinc Transporter), Member 6):

TMED5 (Transmembrane Emp24 Protein Transport Domain Containing 5):

NLRX1 (NLR Family Member X1):

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

TMEM97 (Transmembrane Protein 97):

UBXN8 (UBX Domain Protein 8):

FAR2 (Fatty Acyl CoA Reductase 2):

ERMP1 (Endoplasmic Reticulum Metallopeptidase 1):

F2RL1 (Coagulation Factor II (thrombin) Receptor-Like 1):

GHITM (Growth Hormone Inducible Transmembrane Protein):

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

GPAA1 (GPI Anchor Attachment Protein 1):

ACAD9 (Acyl-CoA Dehydrogenase Family, Member 9):

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

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

ZYG11B (Zyg-11 Family Member B, Cell Cycle Regulator):

TIMM8B (Translocase of Inner Mitochondrial Membrane 8 Homolog B):

MAP7D1 (MAP7 Domain Containing 1):

RBX1 (Ring-Box 1, E3 Ubiquitin Protein Ligase):

TCEB1 (Transcription Elongation Factor B (SIII), Polypeptide 1 (15kDa, Elongin C)):

TCEB2 (Transcription Elongation Factor B (SIII), Polypeptide 2 (18kDa, Elongin B)):

PPT1 (Palmitoyl-Protein Thioesterase 1):

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