SARS-CoV-2 ORF3a Products

SARS-CoV-2 Open Reading Frame 3a (ORF3a) 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 ORF3a is 475 amino acids (aa) with a theoretical molecular weight of 31 kDa (1, 2). The amino acid sequence alignment of SARS-CoV and SARS-CoV-2's ORF3a has 72% sequence identity and 90% sequence similarity (3). Structurally, ORF3a is a homotetramer that is comprised of two non-covalently linked homodimers (2).

The SARS-CoV-2 ORF3a protein encodes for a Ca2+ ion channel that functions in NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome activation (3, 4). The ORF3a ion channel also functions in viral particle release as well as apoptotic and necrotic cell death (5). SARS-CoV-2 ORF3a interacts with the inflammasome component TRAF3 (TNF Receptor Associated Factor 3) which activates ASC (apoptosis-associated speck-like protein contain CARD) ubiquitination and, in-turn, stimulates caspase-1 activation and IL-1beta (interleukin-1-beta) production and maturation (3, 4). IL-1beta activation results in cytokine production and the overproduction of cytokines referred to as a cytokine storm, a hallmark of COVID-19 (4). Additionally, high throughput screening experiments have revealed the SARS-CoV-2 ORF3a binds to the human heme oxygenase (HMOX1) protein (5). HMOX1 has a role in reducing inflammation and tissue damage, both features of SARS-CoV-2 infection (5). The ORF3a-HMOX1 interaction will be worth exploring for its role in innate immune response and as a potential therapeutic target for COVID-19 (5).

Alternative names for SARS-CoV-2 ORF3a includes 2019-nCoV ORF3a protein, COVID-19 ORF3a, Human coronavirus ORF3a protein, ORF3a protein, SARS-CoV-2 accessory protein 3a, SARS-CoV-2 protein 3a, SARS-CoV-2 protein U274, and SARS-CoV-2 protein X1.

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/s12985-020-01402-12. UniProt (P0DTC3)

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. Oladele, J. O., Ajayi, E. I., Oyeleke, O. M., Oladele, O. T., Olowookere, B. D., Adeniyi, B. M., Oyewole, O. I., & Oladiji, A. T. (2020). A systematic review on COVID-19 pandemic with special emphasis on curative potentials of Nigeria based medicinal plants. Heliyon. https://doi.org/10.1016/j.heliyon.2020.e04897

5. Batra, N., De Souza, C., Batra, J., Raetz, A. G., & Yu, A. M. (2020). The HMOX1 Pathway as a Promising Target for the Treatment and Prevention of SARS-CoV-2 of 2019 (COVID-19). International journal of molecular sciences. https://doi.org/10.3390/ijms21176412