The disappearance of ORF8 in human-adapted coronaviruses: the Cheshire cat paradigm

We studied the fate of a gene called ORF8 in different coronaviruses species during their passage to humans. We showed that this gene harbored stop codons in many epidemic SARS-CoV-2 variants in humans and in up to 86% of SARS-CoV-2 circulating in 2023 and therefore could be a non-virulence gene whose disappearance helps the epidemics spread. We questioned whether this is a general phenomenon following coronavirus passage to humans from another species, most often bats. We studied SARS-CoV, SARS-CoV-2, MERS-CoV, and the four coronaviruses endemic in humans for several years or decades and observed gene degradation after species jumps from animals to humans. For SARS-CoV-2, we observed the progressive disappearance of its ORF8 with one or several stop codons and partial or even complete deletions, which is reminiscent of the 'Cheshire cat phenomenon' described in the L. Caroll's Alice's Adventures in Wonderland novel, where a cat gradually disappears to leave only a smile. In viruses that emerged earlier in humans and adapted to this host, only footprints of a few bases remain, but which are significantly associated with the original gene.