The entry of SARS-CoV-2 into host cells, from the full-length genomic RNA (29,903 nt) that serves as an mRNA, the first set of viral proteins are translated from the long (>21 kb) open reading frame ORF1ab (1). The ORF1ab-encoded polyprotein is subsequently processed into 16 individual non-structural proteins (NSP) by two proteases PLpro/nsp3 and 3CLpro/nsp5.
The 3’ half of ORF1ab, ORF1b, encodes a variety of enzymes critical for viral transcription and replication (1). In addition to the genomic RNA, nine major sub-genomic RNAs are produced (1). ORF1a and ORF1b are also separately translated and, as in all coronaviruses, translation of ORF1b in SARS-CoV-2 requires a programmed -1 ribosomal frameshift (-1 PRF) (2).
The genome RNA is packaged by the structural proteins to assemble progeny virions. Shorter sub-genomic RNAs encode conserved structural proteins spike protein (S), an envelope protein (E), membrane protein (M) and nucleocapsid protein (N), and several accessory proteins. SARS-CoV-2 is known to have at least 6 accessory proteins (ORFs 3a, 7, 7a, 7b, 8, and 10)
ProSci Incorporated offers antibodies and recombinant proteins representing most of the SARS-CoV-2 proteome. Below are antibodies and recombinant proteins for each of the SARS-CoV-2 nonstructural proteins.
ProSci offers reagents against open reading frames (ORFs) to excel your research. Explore ProSci’s catalog of ORF (ORF3a to ORF10) antibodies and recombinant proteins:
ORF3a forms homotetrameric potassium sensitive ion channels through Cys133. It contains a cysteine-rich motif (127-133), a tyrosine-based sorting motif YXXΦ (160-163), and a diacidic EXD motif (171-173). In vitro studies have shown that ORF3a induces apoptosis. However, ORF3a inhibits autophagy by sequestering VPS39, a component of HOPS, preventing the HOPS complex from interacting with STX17, thereby blocking assembly of the STX17-SNAP29-VAMP8 SNARE complex which mediates autophagosome/amphiosome fusion with lysosomes, preventing autolysosome formation. ORF3a was implicated in host immune evasion, immunomodulation, and virulence of SARS-CoV via NF-κB, JNK, and cytokine pathways, but this is still under evaluation for SARS-CoV-2. Some studies show that mutation of SARS-CoV-2 ORF3a leads to higher infection and mortality. Deleterious mutations of ORF3a include Q57H, G251 V, P25L, W149L, R126 T, T176I, T217I, D142N, V90F, Y109C, D155Y, Y156N, and K67E.
Explore ProSci’s ORF3a antibodies and recombinant proteins:
| Product | Cat. No. | Application | Clonality | Species |
|---|---|---|---|---|
| SARS-CoV-2 (COVID-19) ORF3a Antibody | 9275 | ELISA | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF3a Antibody (NT) | 10-519 | ELISA, WB | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF3a Antibody (NT1) | 10-520 | ELISA, WB | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF3a Antibody (NT2) | 10-521 | ELISA, WB | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF3a Antibody | 10-533 | ELISA, WB | Polyclonal | Rabbit |
| Product | Cat. No. | Source | Fusion Tag | Sequence |
|---|---|---|---|---|
| SARS-CoV-2 (COVID-19) ORF3a Recombinant Protein | 10-005 | E. Coli | His | 126-275 |
| SARS-CoV-2 ORF3a RP | 20-196 | Bacteria | N-Term MBP Uncleaved | 1 - 298 |
| SARS-CoV-2 ORF3a RP | 20-242 | Bacteria | N-Term GST Uncleaved | 1 - 275 |
ORF3b is a small protein, only comprised of 22 amino acids, but it suppresses activation of type 1 interferons (IFN-I), thereby suppressing the host’s defense against SARS-CoV-2. ORF3b, along with ORF8, elicits the strongest host immune response, and serum antibody levels can be utilized for both early and late-stage SARS-CoV-2 infection.
Explore ProSci’s ORF3b antibodies and recombinant proteins:
| Product | Cat. No. | Application | Clonality | Species |
|---|---|---|---|---|
| SARS-CoV-2 (COVID-19) ORF3b Antibody | 9277 | ELISA, WB | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF3b Antibody | 9279 | ELISA, WB | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF3b Antibody | 9281 | ELISA, WB | Polyclonal | Rabbit |
| Product | Cat. No. | Source | Fusion Tag | Sequence |
|---|---|---|---|---|
| SARS-CoV-2 ORF3b RP | 20-195 | Bacteria | N-Term MBP Uncleaved | 1 - 275 |
| SARS-CoV-2 ORF3b RP | 20-241 | Bacteria | N-Term GST Uncleaved | 1 - 151 |
ORF6 inhibits the type I interferon pathway. It localizes at the nuclear pore complex (NPC) and binds to the Nup98-Rae1 complex, inhibiting nuclear translocation of transcription factors such as STAT and induction of IFN-stimulating genes (IFGs). The C-terminal region of SARS-CoV-2 ORF6 (aa53-61) can suppress IRF3 activation, leading to inhibition of IFN-β production. This region of ORF6 also antagonizes STAT1 nuclear translocation. Inhibition of the IFN-I signaling pathway likely leads to unchecked viral replication in the host. There is still more to be learned about SARS-CoV-2 ORF6; ProSci offers reagents to further research into this protein of interest.
Explore ProSci’s ORF6 antibodies and recombinant proteins:
| Product | Cat. No. | Application | Clonality | Species |
|---|---|---|---|---|
| SARS-CoV-2 (COVID-19) ORF6 Antibody | 9189 | ELISA | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF6 Antibody | 10-515 | ELISA, WB | Polyclonal | Rabbit |
| Product | Cat. No. | Source | Fusion Tag | Sequence |
|---|---|---|---|---|
| SARS-CoV-2 ORF6 RP | 20-193 | Bacteria | N-Term MBP Uncleaved | 1 - 151 |
| SARS-CoV-2 ORF6 RP | 20-240 | Bacteria | N-Term GST Uncleaved | 1 - 61 |
ORF7a is a transmembrane protein that triggers antigen-presenting suppression of CD14+ monocytes and upregulation of proinflammatory cytokines. It may interact with monocytes through an immunoglobulin-like fold containing an integrin-binding site. ORF7a antagonizes IFN-I responses by utilizing the host’s ubiquitin system to enhance this functionality. Ubiquitinated ORF7a suppresses STAT2 phosphorylation, inhibiting the pathway leading to interferon stimulating gene (ISG) transcription. Therefore, ORF7a is involved in both immune evasion and cytokine storm.
Explore ProSci’s ORF7a antibodies and recombinant proteins:
| Product | Cat. No. | Application | Clonality | Species |
|---|---|---|---|---|
| SARS-CoV-2 (COVID-19) ORF7a Antibody | 9283 | ELISA | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF7a Antibody | 9285 | ELISA | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF7a Antibody (NT) | 10-513 | ELISA, WB | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF7a Antibody (CT) | 10-514 | ELISA, WB | Polyclonal | Rabbit |
| Product | Cat. No. | Source | Fusion Tag | Sequence |
|---|---|---|---|---|
| SARS-CoV-2 (COVID-19) ORF7a Recombinant Protein | 10-435 | E. Coli | His | Glu16-Tyr97 |
| SARS-CoV-2 ORF7a RP | 20-239 | Bacteria | N-Term MBP Uncleaved | 1 - 61 |
ORF7b is a membrane protein that has been shown to suppress the IFN-I signaling pathway by blocking the phosphorylation of STAT1 and STAT2. ORF7b has been shown to experimentally form multimers through a leucine zipper, implying that the protein could interfere with host cellular processes which involve leucine-zipper formation.
Explore ProSci’s ORF7b recombinant proteins:
| Product | Cat. No. | Source | Fusion Tag | Sequence |
|---|---|---|---|---|
| SARS-CoV-2 ORF7b RP | 20-194 | Bacteria | N-Term MBP Uncleaved | 1 - 121 |
| SARS-CoV-2 ORF7b RP | 20-238 | Bacteria | N-Term GST Uncleaved | 1 - 43 |
ORF8 is part of a hypervariable region of the SARS-CoV-2 genome, potentially aiding in viral host adaptation. The protein forms dimers and despite being immunogenic, is involved in viral immune evasion and suppression.
ORF8 is a 121 amino acid protein containing a signal sequence as well as a predicted immunoglobulin-like fold, which could aid in interacting with the host immune system. ORF8 can be found in the lumen of the ER, upregulating the expression of ER chaperones for protein folding, as well as in a secreted form.
Within the ER lumen, it interacts with factors involved in ER-associated degradation. SARS-CoV-2 ORF8 can downregulate MHC-I in cells, inhibiting the presentation of viral antigens. ORF8 also acts as an IFN-I agonist, furthering its role in immune evasion. Detecting host antibodies against ORF8, along with ORF3b, can be utilized for diagnostics of both early and late-stage SARS-CoV-2 infection. ProSci has developed ORF8 antibodies to further research in uncovering details of how ORF8 promotes viral replication and evasion of the host innate immune system.
Explore ProSci’s ORF8 antibodies and recombinant proteins:
| Product | Cat. No. | Application | Clonality | Species |
|---|---|---|---|---|
| SARS-CoV-2 (COVID-19) ORF8 Antibody | 9287 | ELISA, WB | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF8 Antibody | 9289 | ELISA, WB | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF8 Antibody (IN) | 10-511 | ELISA, WB | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF8 Antibody (CT) | 10-512 | ELISA, WB | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF8 Antibody | 10-532 | ELISA, WB | Polyclonal | Rabbit |
| Product | Cat. No. | Source | Fusion Tag | Sequence |
|---|---|---|---|---|
| SARS-CoV-2 (COVID-19) ORF8 Protein | 10-002 | E. Coli | His | 16-121 |
| SARS-CoV-2 (COVID-19) ORF8 Recombinant Protein | 10-436 | E. Coli | His | Phe16-IIe121 |
| SARS-CoV-2 ORF8 RP | 20-192 | Bacteria | N-Term MBP Uncleaved | 1 - 43 |
| SARS-CoV-2 ORF8 RP | 20-237 | Bacteria | N-Term GST Uncleaved | 1 - 121 |
Explore ProSci’s ORF9a recombinant proteins:
| Products | Cat. No. | Source | Fusion Tag | Sequence |
|---|---|---|---|---|
| SARS-CoV-2 ORF9a RP | 20-191 | Bacteria | N-Term MBP Uncleaved | 1 - 121 |
| SARS-CoV-2 ORF9a RP | 20-236 | Bacteria | N-Term GST Uncleaved | 1 - 97 |
ORF9b suppresses the innate immune response by interacting with various host proteins. It targets NEMO (IKKγ), an essential modulator of NF-κB, inhibiting IKKα/β/γ-NF-κB signaling and IFN production. SARS-CoV-2 ORF9a has also been shown to interact with TOM70 on mitochondria, blocking IFN-I activation, and thereby blocking host immune response. ORF9b immediately accumulates in cell models, indicating it is an early inhibitor of the immune response.
Explore ProSci’s ORF9b antibodies and recombinant proteins:
| Products | Cat. No. | Application | Clonality | Species |
|---|---|---|---|---|
| SARS-CoV-2 (COVID-19) ORF9b Antibody | 9191 | ELISA | Polyclonal | Rabbit |
| Product | Cat. No. | Source | Fusion Tag | Sequence |
|---|---|---|---|---|
| SARS-CoV-2 (COVID-19) ORF9b RP | 20-190 | Bacteria | N-Term MBP Uncleaved | 1 - 97 |
| SARS-CoV-2 (COVID-19) ORF9b RP | 20-235 | Bacteria | N-Term GST Uncleaved | 1 - 73 |
ORF9c membrane protein. There is not much known about this protein aside from its unstable nature. Early studies of ORF9c with an epithelial lung cell line indicate it may be involved in coordinating cellular changes essential to the SARS-CoV-2 life cycle as well as in immune evasion. It appears that ORF9c interferes with interferon (IFN) signaling as IFNL1, IFNA, IRF7, IRF1, INFAR, and other IFN signaling protein levels were reduced. ORF9c also appears to affect antigen presentation as HLA proteins, for example, were decreased in the presence of ORF9c. In addition, IL-1, IL-6, and p38 MAPK signaling pathways were upregulated in the presence of ORF9c. As such, ORF9c may be involved in the immune escape of SARS-CoV-2 virus-infected cells.
Explore ProSci’s ORF9c antibodies:
| Products | Cat. No. | Application | Clonality | Species |
|---|---|---|---|---|
| SARS-CoV-2 (COVID-19) ORF9c Antibody | 9291 | ELISA | Polyclonal | Rabbit |
ORF10 was originally identified as the tenth open reading frame in the SARS-CoV-2 genome and initially raised a lot of questions as it did not share sequence homology with any known protein. It has since been determined that the protein is not essential for replication and the virus retains full functionality when the ORF10 is without the gene.
Explore ProSci’s ORF10 antibodies and recombinant proteins:
| Products | Cat. No. | Application | Clonality | Species |
|---|---|---|---|---|
| SARS-CoV-2 (COVID-19) ORF10 Antibody | 9293 | ELISA | Polyclonal | Rabbit |
| SARS-CoV-2 (COVID-19) ORF10 Antibody | 10-507 | ELISA, WB | Polyclonal | Rabbit |
| Product | Cat. No. | Source | Fusion Tag | Sequence |
|---|---|---|---|---|
| SARS-CoV-2 ORF10 RP | 20-189 | Bacteria | N-Term MBP Uncleaved | 1 - 73 |
| SARS-CoV-2 ORF10 RP | 20-234 | Bacteria | N-Term GST Uncleaved | 1 - 38 |
