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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 ones^4,5,6.

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 response, the most important innate antiviral cytokines.

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 Spike Subunit S1 Protein, SARS-CoV-2 Subunit S2 Protein

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

SARS-CoV-2 Antibodies: anti-SARS-CoV-2 Antibodies

SARS-CoV Viral Proteins: , , , ,

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).