key: cord-0928598-xlujmq1l authors: Zandi, Milad title: ORF8a as a viroporin in SARS-CoV-2 infection? date: 2021-08-02 journal: Cytokine Growth Factor Rev DOI: 10.1016/j.cytogfr.2021.07.002 sha: f476639d71d3d04570f48ecc46fb807301d371f5 doc_id: 928598 cord_uid: xlujmq1l nan Cytokine and Growth Factor Reviews xxx (xxxx) xxx Please cite this article as: Milad Zandi, Cytokine and Growth Factor Reviews, https://doi.org/10.1016/j.cytogfr.2021.07.002 Available online 2 August 2021 1359-6101/© 2021 Elsevier Ltd. All rights reserved. The seventh human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is described as the causative agent of coronavirus infectious disease (COVID-19) [1] . Since the first detection of SARS-CoV-2 in late December 2019 [2] , the virus and ongoing COVID-19 pandemic have spread across the globe, killing more than 4 million individuals in the past 18 months. Highly efficacious vaccines generated by biotech and pharma remain the only solution to this international crisis. The SARS-CoV-2 harbors a positive-sense single-stranded RNA in order of 5 ′ -replicase (ORF1a/b)-S-E-M-N-poly(A)-3 ′ , also the SARS-CoV-2 genome contains several ORFs at its 3 ′ portion which encodes accessory proteins including ORF3a, ORF3b, ORF6, ORF7a, ORF7b, ORF8, ORF9b, ORF9c as well as ORF10 [3, 4] . The scientific evidence shows that the genome of SARS-CoV-2 lacks ORF8a [5] [6] [7] [8] . Indeed, both ORF8a and ORF8b are absent in SARS-CoV-2 because of a 29-nucleotide deletion that inactivates the formation ORF8ab tandem [9] , while ORF8a and ORF8b are present in SARS-CoV [5, 10] . In SARS-CoV, ORF8 splitting into two separated ORFs (ORF8a and ORF8b) [11] . In addition, ORF3b of SARS-CoV is longer than its ortholog in SARS-CoV-2 [8, 12] . The SARS-CoV-2 encodes an intact ORF8, which among all the viral proteins of SARS-CoV-2 and SARS-CoV shares the least homology [13] . The ORF8 protein, one of the accessory proteins of SARS-CoV-2, can downregulate surface and total levels of MHC-1 by direct binding and can also degrade MHC-1 by the autophagy pathway [13] . In addition, the ORF8 protein prevents antigen presentation system and CTL-mediated killing of cells that infected with SARS-CoV-2 [14, 15] . I have recently read with interest an article by Ni Zhao et al. the authors reported that SARS-CoV-2 can encode a set of accessory proteins, including two ion-channel proteins known as viroporins (open reading frame 3a (ORF3a) and ORF8a) [16] , while according to scientific evidence, SARS-CoV-2 lacks ORF8a, and this protein (ORF8a) has no role in SARS-CoV-2 infection. The author reports no declarations of interest. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19)-anatomic pathology perspective on current knowledge Diabetes and coronavirus infections Molecular simulation-based investigation of highly potent natural products to abrogate formation of the nsp10-nsp16 complex of sars-cov-2 A systemic and molecular study of subcellular localization of SARS-CoV-2 proteins Structural characterization of SARS-CoV-2: where we are, and where we need to be SARS-CoV-2: an overview of virus genetics, transmission, and immunopathogenesis SARS-CoV-2 ORF8 forms intracellular aggregates and inhibits IFNγinduced antiviral gene expression in human lung epithelial cells Coronavirus biology and replication: implications for SARS-CoV-2 Atypical divergence of SARS-CoV-2 Orf8 from Orf7a within the coronavirus lineage suggests potential stealthy viral strategies in immune evasion Virus against Virus: a Potential Treatment for 2019-nCov (SARS-CoV-2) and Other RNA Viruses Structural characterization of SARS-CoV-2: where we are, and where we need to be Interplay between SARS-CoV-2 and the type I interferon response The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-I Immune evasion via SARS-CoV-2 ORF8 protein? The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-І The NLRP3 inflammasome and COVID-19: activation, pathogenesis and therapeutic strategies