SARS-CoV-2 ORF7a Products

SARS-CoV-2 Open Reading Frame 7a (ORF7a) is one of the nine downstream accessory protein open reading frames of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 (1). SARS-CoV-2 ORF7a is a type I transmembrane protein with a 121 amino acid (aa) sequence and a theoretical molecular weight of 13.7 kDa (2, 3). ORF7a localizes mostly on the Golgi apparatus but also presents on the cell surface (4). The N-terminal domain of ORF7a is comprised of 7 beta-strands that form 2 beta-sheets, arranged by an immuno-globulin-like beta-sandwich fold (2, 5). The aa sequence alignment of SARS-CoV and SARS-CoV-2's ORF7a has 85.2% sequence identity and 95.9% sequence similarity (3).

Similar to its role in SARS-CoV, ORF7a of SARS-CoV-2 is an inhibitor of the host tetherin bone marrow stromal antigen-2 (BST-2) (2, 4). Functionally, ORF7a binds to BST-2, inhibiting its viral restriction activity by blocking glycosylation (2, 4).

References

1. Michel, C. J., Mayenr, C., Poch, O., & Thompson, J. D. (2020). Characterization of accessory genes in coronavirus genomes. Virology journal. https://doi.org/10.1186/s12985-020-01402-1

2. UniProt (P0DTC7)

3. 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. https://doi.org/10.1007/s10930-020-09901-4

4. Taylor, J. K., Coleman, C. M., Postel, S., Sisk, J. M., Bernbaum, J. G., Venkataraman, T., Sundberg, E. J., & Frieman, M. B. (2015). Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference. Journal of virology. https://doi.org/10.1128/JVI.02274-15

5. Nelson, C. A., Pekosz, A., Lee, C. A., Diamond, M. S., & Fremont, D. H. (2005). Structure and intracellular targeting of the SARS-coronavirus Orf7a accessory protein. Structure (London, England : 1993). https://doi.org/10.1016/j.str.2004.10.010