SARS-CoV-2 CQ.1 and CQ.1.1 lineage isolates: 100% synonymous base substitution at furin arginine CGG–CGG codons

Abstract The SARS‐CoV2 spike glycoprotin S1/S2 junction not only has no analogy in other becoronaviruses, including neither the Laos closest known relatives, but also it has two arginine codons CGG–CGG, whose usage is extremely rare in coronaviruses. The 12-nt SARS-CoV-2 S gene insert having that CGG–CGG genetic footprint 100% match to several human mRNA RefSeq transcripts which are located in exons of ubiquitous and highly expressed genes or specific genes of target human tissues of virus infection. An hypothesis for the probable human origin of the S1/S2 junction polybasic motif (originally PRRA) includes that it has been acquired by recombination between the genome of a SARS-CoV-2 progenitor and mRNA transcripts within human infected cells. Since the furin arginine pair is essential for virus infection to human cells and arginine has six codons SARS-CoV-2 can optimize the CGG–CGG codons. Here I show that in a sample of the available GISAID SARS-CoV-2 CQ.1 (516) and CQ.1.1 (117) lineage isolates the 100% of them showed synonymous base substitution at this position. The CGG–CGG footrprint to have changed to CGT–CGG. The location of the CQ.1 lineage isolates was: Asia 8.30% (45 isolates), Europe 76.57% (415), North America 6.64% (36), Oceania 8.30% (45) and South America 0.18% (1). That of CQ.1.1 lineage isolates was: Europe 45.6% (57) and North America 54.4 (68). Based on NCBI Virus database SARS-CoV-2 lineages associated to spike glycoprotein sequences I created a SARS-CoV-2 lineage ranking the from earliest CQ.1 date (August 30, 2022) up to date. Of 418,257 records, there were 1,165 distinct lineages. Ranking positions for CQ.1 and CQ.1.1 lineages were 582 and 506, respectivaly, both in the second quartile. These results coincide with those obtained previosly in SARS-CoV-2 CQ.2 and EE.2 lineage isolates. Everything points to that through evolution SARS-CoV-2 adapts the extremely rare CGG–CGG footprint to its own genomic parameters, thereby also erasing an evidence on its origin.