Research Resources for SARS-CoV-2 Non-Structural and Accessory Proteins
SARS-CoV-2 Research Resources
After SARS-CoV-2 enters the host cell the viral genomic RNA is translated from two open reading frames (ORFs), ORF1a and ORF1b. The encoded polypeptides, pp1a and pp1ab, are further processed to produce 11 and 16 non-structural proteins (nsps), respectively. These nsps are required for viral replication and pathogenesis. In addition to primary translation, subgenomic RNAs (sgRNAs) are generated by discontinuous transcription and deletions, allowing for translation of both the structural and ORF accessory proteins. The 9 ORF accessory proteins appear to have diverse roles involving host-virus interactions and viral pathogenesis. While the main structural proteins (Spike, Nucleocapsid, Envelope and Membrane) have been well characterized, the ORF accessory proteins and nsps are in general less understood.
What are SARS-CoV-2 Non-structural Proteins?
Non-structural proteins (nsps) serve different functions in the viral replication cycle. Together the encoded nsps (1-16) form a replicase-transcriptase complex.
| Non-structural Proteins (nsps) | % Identity SARS-CoV vs SARS-CoV-2 | Properties and Functions |
|---|---|---|
| nsp1 | 84% | Suppression of host gene expression |
| nsp2 | 100% | Suppression of host gene expression |
| nsp3 | 76% | Multi-spanning transmembrane protein; papain-like protease domain; mediates cleavage of ORF encoded polypeptides |
| nsp4 | 80% | Multi-spanning transmembrane protein; important for membrane rearrangement |
| nsp5 | 96% | Papain-like protease domain; mediates cleavage of ORF encoded polypeptides |
| nsp6 | 88% | Multi-spanning transmembrane protein; associates with nsp3 and nsp4 to form organelle-like structure (double membrane vesicle) for viral replication; induces autophagy and formation of Atg5 and LC3 containing vesicles |
| nsp7-nsp8 | 96% | Primase complex |
| nsp9 | 99% / 97% | RNA binding protein; forms dimer important in viral infection |
| nsp10 | 97% | Contains two zinc finger domains; cofactor for the activation of the replicative enzyme |
| nsp11 | 96% | RNA-dependent RNA polymerase activity (RdRP); mediates genome replication |
| nsp12 | 96% | Helicase activity/triphosphatase; RNA and DNA unwinding activity; involved in viral replication |
| nsp13 | 99% | Exoribonuclease activity |
| nsp14 | 95% | Papain-like protease domain; mediates cleavage of ORF encoded polypeptides |
| nsp15 | 89% | Endoribonuclease activity |
| nsp15 | 93% | Methyltransferase activity |
SARS-CoV-2 Recombinant Proteins
| Recombinant Proteases | Region of Full-Length Protein |
|---|---|
| Papain-like Protease [E-611-050] | 746-1060 aa |
| SARS-CoV-2 3CL Protease | 1-306 aa |
Antibodies to SARS-CoV-2 Open Reading Frames (ORF) Accessory Proteins
We offer antibodies to the Open Reading Frame (ORF) Accessory Proteins of SARS-CoV-2 including ORF3a, ORF6, OFR7a, ORF8, and ORF10. Although the sequence identity for most accessory protein ORFs is greater than 85% between SARS-CoV-2 and SARS-CoV, ORF3, ORF8, and ORF10 show less similarity. The functionality of the SARS-CoV-2 ORF accessory proteins varies widely, though they all contribute to viral pathogenesis. These antibodies have been validated for use in ELISA and WB.
| Open Reading Frame (ORF) | Properties and Functions |
|---|---|
| ORF1a | Encodes for polyprotein 1a which is processed to nsp1 – nsp11 |
| ORF3a |
Interacts with cellular vesicle trafficking and may modify endomembrane compartments to promote viral replication Binds TRIM59, role in innate immunity signaling ORF3a of SARS-CoV-2 and SARS-CoV has pro-apoptotic activity |
| ORF6 | A role in viral pathogenesis; has been shown to interact with nsp8, the non-structural protein that functions in promoting RNA polymerase activity |
| ORF7a | Type I transmembrane protein |
| ORF8 | Role in MHC I downregulation and inhibition of interferon signaling that may point to SARS-CoV-2 functioning in virus-host processes through macromolecule interactions |
| ORF10 | Reported to interact with members of Cullin 2 RING E3 ligase complex and therefore may play a role in ubiquitination and degradation of restriction factors |
-
Ahmadpour, D., & Ahmadpoor, P (2020) How the COVID-19 Overcomes the Battle? An Approach to Virus Structure Iranian journal of kidney diseases
-
Angelini, M. M. et al. (2013) Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles. MBio
-
Gordon, D. E. et al. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing Nature
-
Kim, D. et al. (2020) The architecture of SARS-CoV-2 transcriptome Cell
-
Mohammad, S et al. (2020) SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: Genomic Divergence and Functional Convergence Pathogens
-
Prajapat, M. et al. (2020) Drug targets for corona virus: A systematic review Indian Journal of Pharmacology
-
Ren, Y. et al. (2020) The ORF3a protein of SARS-CoV-2 induces apoptosis in cells Cellular & molecular immunology
-
Wu, C. (2020) . Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods Acta Pharmaceutica Sinica B
-
Yoshimoto F. K (2020) The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19. The Protein Journal