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 acquisition of the polybasic furin cleavage site on the S protein in one of its closest relatives. The recent discovery in Laos of bat Rhinolophus coronaviruses that contain receptor binding domains almost identical to that of SARS-CoV-2, and despite not having the furin site, they can therefore infect human cells (1), is the cornerstone to identify the SARS-CoV-2 progenitor. However, it is not yet known where the insertion of the furin site at the S1/S2 junction in the S protein of the pandemic virus came from. Not only from where, but also how, where and when of such acquisition. The most surprising was: ( i ) that the polybasic furin cleavage site is unique to SARS-CoV-2 among Sarbecovirus (2), and ( ii ) that the inserted four amino acid motif has a CGG-CGG encoded arginine pair which is rare in coronaviruses (3). So, my question is if the SARS-CoV-2 insert in the S gene insert would match to human transcripts. Here, I address this issue by using NCBI and GISAID databases, the NCBI Human Genome Resources, sequence analysis tools and in-house developed bioinformatic 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 the expression patterns their genes, results provide insight into human potential recombination link to SARS-CoV-2 furin cleavage site, during undetected human-to-human virus transmission.