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SARS-CoV-2 Protein Interactome

SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA beta coronavirus belonging to the order of nidovirales. In the first three months since its initial identification in December 2019 SARS-CoV-2 has caused more than 800.000 confirmed cases and over 40.000 fatalities worldwide of the associated severe acute respiratory syndrome COVID-19 (coronavirus disease 2019)1.

Presently, no vaccine is available to curb the virus’ spread. A potential source for COVID-19 therapeutics are existing antiviral reagents that are either already approved or in development for the treatment of the other two respiratory syndromes – SARS and MERS – caused by human coronaviruses (hCoVs)2,3. A deeper understanding of the function of the virus and its proteins is essential for the targeted application of existing drugs and the discovery of new ones4,5,6.

The 30kb SARS-CoV-2 genome encodes 16 non-structural proteins (Nsp1-16), four structural proteins (spike, envelope, nucleocapsid, membrane), and nine putative accessory factors7. Many of these proteins and polypeptides have a number or interaction partners in particular in lung cells, the virus’ primary infection site. These interactions with the host cell determine the virus’ ability to infect the cell, reproduce its genome and trigger the production and release of new virus particles. In addition, several virus proteins appear to have interaction partners affecting innate immune pathways such as the interferon signaling pathway, NF-kappa B inflammatory response, type I interferon production, and IRF-3 activation.

At least some of the members of the third group of SARS-CoV-2 proteins, the nine accessory factors (Orf3a-10), have been implicated in driving progression of COVID-19. Orf3a induces apoptosis and is thought to activate NF-kB and the NLRP3 inflammasome involved in pyroptosis, a highly inflammatory form of apoptosis. The type I interferon (IFN) antagonists Orf6 and Orf9b inhibit the IFN alpha and beta signaling, two key players of the antiviral innate immune response.

Some of these regulatory functions are shared with other pathogenic human viruses. Therefore, a deeper understanding of these mechanisms may lead to the identification of targets and development of novel therapeutics relevant for future virus pandemics.

SARS-CoV-2 Structural Proteins: 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 Antibodies: anti-SARS-CoV-2 Antibodies

Additional information and products: CoV-2 Resource, SARS-CoV-2 RT-PCR and qPCR Kits, SARS-CoV-2 ELISA Kits, SARS-CoV-2 Life Cycle Stages & Inhibition Targets

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

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)):

IDE (Insulin-Degrading Enzyme):

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):

rala (Ras-related Protein Ral-A):

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):

HOOK1 (Hook Homolog 1):

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

ARF6 (ADP-Ribosylation Factor 6):

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)):

ERO1LB (ERO1-Like beta):

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):

DPH5 (DPH5 Homolog):

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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