The ORF3a accessory protein has the ability to trigger apoptosis in SARS-CoV, prompting investigations into its role in SARS-CoV-2. The pro-apoptotic effect of the SARS-CoV-2 ORF3a protein was confirmed in Vero E6, HepG2, and HEK293T cells using staining methods and by tracking key molecules involved in apoptosis pathways.

Role of SARS-CoV-2 ORF3a in Inducing Apoptosis

Co-occurring mutations have been observed between ORF3a and the region encoding the (S) spike glycoprotein and this may indicate some form of relation in the functions of the S protein and the ORF3a protein. One major function of the ORF3a protein seems to be in apoptosis (or “programmed cell death”) of host cells which will be discussed in further nodes.

Ohio State University, Columbus

Similar to other accessory proteins, ORF3a plays an important role in the virulence of SARS-CoV2 including affecting the host antiviral response. ORF3a codes for a protein that is made of 274 amino acids and three regions: an ion channel, CBM (Caveolin Binding Motif), and TNF Receptor Associated Factor (TRAF). 

Structure of ORF3a Accessory Protein

Hassan, S. S., Choudhury, P. P., Basu, P., & Jana, S. S. (2020). Molecular conservation and Differential mutation on ORF3a gene in Indian SARS-CoV2 genomes. Genomics.

Molecular conservation and Differential mutation on ORF3a gene in Indian
SARS-CoV2 genomes


Ren, Y., Shu, T., Wu, D. et al. The ORF3a protein of SARS-CoV-2 induces apoptosis in cells. Cell Mol Immunol 17, 881–883 (2020). https://doi.org/10.1038/s41423-020-0485-9

The ORF3a protein of SARS-CoV-2 induces apoptosis in cells

Conserved Motifs in proteins can be quite beneficial as they may provide insights into the function and structural properties of the protein. In the case of the ORF3a Protein, three conserved motifs were observed:
- Cysteine-rich motif
- SGD motif
- Tyrosine-based motif

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