Relation between ORF8a and the mitochondrial protein TOM70 in SARS-CoV-2 infection.

The genome of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has two large open reading frames (ORFs): ORF1a and ORF1ab. At the 5′ end of genome encodes polyproteins that are processed into 16 non‐structural proteins (nsp1‐nsp16) by proteolytic enzymes, the Mpro (3CLpro) and the papain‐like protease PLpro. The accessory proteins and four structural proteins including: spike (S), membrane (M), envelope (E) and nucleocapsid (N) are encoded by the 3′ end of the SARS‐CoV‐2 genome. The genome of SARS‐CoV‐2 is similar to SARS‐CoV except for the 3′ open reading frame: SARS‐CoV encodes ORF8a and ORF8b, however, ORF8 of the novel coronavirus is intact.

The SARS‐CoV‐2 contains a single ORF8 protein which is various from SARS‐CoV which has two ORF8s (ORF8a and ORF8b). ORF8 is considered as one of the most relevant genes that have previously reported as genetic change during human‐to‐human transmission of the SARS‐CoV epidemic. No motif such as VLVVL (75‐79aa) or known functional domain has been observed in the ORF8 of SARS‐CoV‐2 that activates the nucleotide‐binding domain and leucine‐rich repeat‐containing protein 3 (NLRP3) inflammasomes or bind to the interferon regulatory factor (IRF) domain (IAD) region of IRF3 then inactivates interferon signalling.

We read with interest a review by Dr Lessi et al The authors stated that recent findings demonstrated that SARS‐CoV‐2, such as SARS‐CoV virus, in addition to ORF7a and ORF8a, also expresses ORF9b4 that can be associated with the mitochondrial protein TOM70, impairing antiviral responses, however, according to evidence, in contrast to the SARS‐CoV, ORF8a is absent in SARS‐CoV‐2 and has no role in activate inflammasomes through NLRP3 in COVID‐19 pathogenesis, and this is one of the important differences between SARS‐CoV‐2 and SARS‐CoV.

CONFLICT OF INTEREST

The authors declare no conflict of interest.