Abstract

RNA viruses are very mutation prone. We recently reported SARS-CoV-2 ORF8 gene CAA=TAA and AAA=TAA Termination Codon Mutations in B.1.1.7 variants with no production of viable ORF8 protein. We described here another GGA=TGA termination codon in the 8th codon of ORF8 gene located exclusively in XBB.1 (XBB.1.16 and XBB.1.22) and XBB.1.5 subvariants (XBB.1.5.1 to XBB.1.5.39) but not in XBB.2 variant or Alpha, Beta, Gamma, Delta and Omicron BA.1, BA.2, BA.4, BA.5, BF.7 and BQ.1 subvariants. However, G>T mutation at 27915 also created an alternate ATG codon but the protein product was short due to preceding TAG and TGA termination codons. The originally located following ATG codons were there but in alternate reading frames and ultimately no ORF8 protein was formed in XBB.1.5 subvariants which were spreading highly now over BA.2.75, BA.4.6, BA.5.2.1, BF.7 and BQ.1.1 subvariants. This is a vivid example of three termination codon mutations in the coronavirus ORF8 protein which was implicated as target for many human proteins regulating interferon production, chromosome instability, antibody production, patho genicity and virus clearance. The 30nt deletion in the 3’-UTR, including 24LPP, and 145Y deletions in Spike protein as well as N-protein 31ERS and ORF1ab polyprotein 3675SGF deletions made XBB.1.5 Omicron coronavirus weak and less pathogenic so that WHO declared coronaviruses as non-emergency pathogen.

Keywords:Termination codon mutants; ORF8 protein; COVID-19; Immunomodulation; Higher transmission; Lower pathogenicity