The accessory factor 3a is encoded by ORF3a located in between the S and E genes and is the largest accessory protein of SARS-CoV-2. ORF3a forms homotetrameric Ca2+/K+ sensitive ion channels (viroporin) in the host cell membrane and may modulate virus release. ORF3a promotes membrane rearrangement and cell apoptosis; it induces vesicle formation and is necessary for SARS-CoV-2-induced Golgi fragmentation. It is also involved in pathogenesis by expression of fibrinogen subunits FGA, FGB, and FGG in host lung epithelial cells. It has also been found to activate NF-kappaB and the NLRP3 inflammasome by promoting TNF receptor-associated factor 3 (TRAF3)-dependent ubiquitination of p105 and ASC.

MDLFMRIFTIGTVTLKQGEIKDATPSDFVRATATIPIQASLPFGWLIVGVALLAVFQSASKIITLKKRWQLALSKGVHFVCNLLLLFVTVYSHLLLVAAGLEAPFLYLYALVYFLQSINFVRIIMRLWLCWKCRSKNPLLYDANYFLCWHTNCYDYCIPYNSVTSSIVITSGDGTTSPISEHDYQIGGYTEKWESGVKDCVVLHSYFTSDYYQLYSTQLSTDTGVEHVTFFIYNKIVDEPEEHVQIHTIDGSSGVVNPVMEPIYDEPTTTTSVPL

275 aa; 150 kDa