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SARS-CoV-2 Protein Interactome

Written/Edited by Dr. Stefan Pellenz PhD

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


  1. Dong, Du, Gardner: "An interactive web-based dashboard to track COVID-19 in real time." in: The Lancet. Infectious diseases, Vol. 20, Issue 5, pp. 533-534, (2020) (PubMed).
  2. Morse, Lalonde, Xu, Liu: "Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV." in: Chembiochem : a European journal of chemical biology, Vol. 21, Issue 5, pp. 730-738, (2020) (PubMed).
  3. Li, De Clercq: "Therapeutic options for the 2019 novel coronavirus (2019-nCoV)." in: Nature reviews. Drug discovery, Vol. 19, Issue 3, pp. 149-150, (2020) (PubMed).
  4. Báez-Santos, St John, Mesecar: "The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds." in: Antiviral research, Vol. 115, pp. 21-38, (2015) (PubMed).
  5. Kirchdoerfer, Ward: "Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors." in: Nature communications, Vol. 10, Issue 1, pp. 2342, (2019) (PubMed).
  6. Coutard, Valle, de Lamballerie, Canard, Seidah, Decroly: "The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade." in: Antiviral research, Vol. 176, pp. 104742, (2020) (PubMed).
  7. Gordon, Jang, Bouhaddou, Xu, Obernier, O'Meara, Guo, Swaney, Tummino, Hüttenhain, Kaake, Richards, Tutuncuoglu, Foussard, Batra, Haas, Modak, Kim, Haas, Polacco, Braberg, Fabius, Eckhardt, Soucheray, Bennett, Cakir, McGregor, Li, Naing, Zhou, Peng, Kirby,: "A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing." in: bioRxiv : the preprint server for biology, (2020) (PubMed).

CoV-2 Spike Protein

CoV-2 Nucleocapsid Protein

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

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):

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):

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):

TUBGCP2 (Tubulin, gamma Complex Associated Protein 2):

PMPCA (Peptidase (Mitochondrial Processing) alpha):

TARS2 (threonyl-tRNA Synthetase 2, Mitochondrial):

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):



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

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





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

ATP13A3 (ATPase Type 13A3):

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


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

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

QSOX2 (Quiescin Q6 Sulfhydryl Oxidase 2):

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):


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):


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):


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

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



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

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):


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 Protein 3):

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)):

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

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

CEP250 (Centrosomal Protein 250kDa):

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):





VPS39 (Vacuolar Protein Sorting 39 Homolog):

VPS11 (Vacuolar Protein Sorting 11 Homolog):

SUN2 (Sad1 and UNC84 Domain Containing 2):

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



HEATR3 (HEAT Repeat Containing 3):

MDN1 (MDN1, Midasin Homolog):


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):

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

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

PCSK6 (Proprotein Convertase Subtilisin/kexin Type 6):



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):

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):


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