SARS-CoV-2 Open Reading Frames (ORFs)


Diagram of ProSci ORF Antibodies against SARS-CoV-2 Proteome


The SARS-CoV-2 virus which causes COVID-19 is comprised of 10 open reading frames (ORFs). Many of these create structural proteins and nonstructural proteins, but several of them generate unique proteins named after the ORF they are encoded by. Inhibiting some of these SARS-CoV-2 proteins which contribute to viral immune evasion could lead to faster clearing of SARS-CoV-2 infection by improving the host’s antiviral systems. ProSci has catalog antibodies and recombinant proteins to many of the SARS-CoV-2 ORF accessory proteins.


ORF3a Antibodies & 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 autophagasome/amphiosome fusion with lysomes, 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.

ORF3a Antibodies

ProductCat. No.ApplicationClonalitySpecies
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

ORF3a Protein

ProductCat. No.SourceFusion TagSequence
SARS-CoV-2 (COVID-19) ORF3a Recombinant Protein 10-005 E. Coli His 126-275


ORF3b

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, elicit the strongest host immune response and serum antibody levels can be utilized for both early and late stage SARS-CoV-2 infection.

ProductCat. No.ApplicationClonalitySpecies
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


ORF6 Antibodies

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.

ProductCat. No.ApplicationClonalitySpecies
SARS-CoV-2 (COVID-19) ORF6 Antibody 9189 ELISA Polyclonal Rabbit
SARS-CoV-2 (COVID-19) ORF6 Antibody 10-515 ELISA, WB Polyclonal Rabbit


ORF7a Antibodies & Proteins

ORF7a is a transmembrane protein which 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 ubiqutin 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.

ORF7a Antibodies

ProductCat. No.ApplicationClonalitySpecies
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

ORF7a Protein

ProductCat. No.SourceFusion TagSequence
SARS-CoV-2 (COVID-19) ORF7a Recombinant Protein 10-435 E. Coli His Glu16-Tyr97


ORF7b

ORF7b is a membrane protein which has been shown to suppress the IFN-I signaling pathway by blocking 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.


ORF8 Antibodies & Proteins

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 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 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.

ORF8 Antibodies

ProductCat. No.ApplicationClonalitySpecies
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

ORF8 Proteins

ProductCat. No.SourceFusion TagSequence
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


ORF9b Antibodies

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.

ProductsCat. No.ApplicationClonalitySpecies
SARS-CoV-2 (COVID-19) ORF9b Antibody 9191 ELISA Polyclonal Rabbit


ORF9c Antibodies

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 immune escape of SARS-CoV-2 virus infected cells.

ProductsCat. No.ApplicationClonalitySpecies
SARS-CoV-2 (COVID-19) ORF9c Antibody 9291 ELISA Polyclonal Rabbit


ORF10 Antibodies

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 without the gene.

ProductsCat. No.ApplicationClonalitySpecies
SARS-CoV-2 (COVID-19) ORF10 Antibody 9293 ELISA Polyclonal Rabbit
SARS-CoV-2 (COVID-19) ORF10 Antibody 10-507 ELISA, WB Polyclonal Rabbit


ProSci is committed to furthering global research efforts to understand this novel virus and the disease it causes by offering a broad catalog of SARS-CoV-2 antibodies, recombinant proteins, and related research reagents. By offering reagents to viral accessory proteins, ProSci supports research into unique approaches in diagnostics (e.g. measuring patient serum antibody levels of ORF3b and ORF8) and therapeutics (e.g. inhibiting some of the accessory proteins can aid in overcoming immune evasion and suppression). Contact us to see how we can help.


References