Evidence-based analysis of the SARS-CoV-2 furin site origin

Abstract The origin of the SARS-CoV-2 is still unclear. Simply said, its emergence is due to the acquisitionof the polybasic furin cleavage site on the S protein in one of its closest relatives. The recentdiscovery in Laos of bat Rhinolophus coronaviruses that contain receptor binding domains almostidentical to that of SARS-CoV-2, and despite not having the furin site, they can therefore infecthuman cells (1), is the cornerstone to identify the SARS-CoV-2 progenitor. However, it is not yetknown where the insertion of the furin site at the S1/S2 junction in the S protein of the pandemicvirus came from. Not only from where, but also how and when of such acquisition. The mostsurprising was: (i) that the polybasic furin cleavage site is unique to SARS-CoV-2 amongSarbecovirus (2), and (ii) that the inserted four amino acid motif has a CGG-CGG encoded argininepair which is rare in coronaviruses (3). So, my question is if the SARS-CoV-2 insert in the S geneinsert would match to human transcripts. Here, I address this issue by using NCBI and GISAIDdatabases, the NCBI Human Genome Resources, sequence analysis tools and in-house developedbioinformatic tools. I found that the 12-nucleotide insert encoding SARS-CoV-2 furin site 100%match to several human transcripts. Taken together the presence of these human transcripts and theexpression patterns their genes, results provide insight into human potential recombination link toSARS-CoV-2 furin cleavage site, during undetected human-to-human virus transmission. OtherPRRA-like insertions in the SARS-CoV-2 spike protein are shown.