SARS-CoV-2 isolates missing part of the furin cleavage site

Abstract

The discovery ofbat coronaviruses in Southeast Asia very similar to SARS-CoV-2 is key to deciphering SARS-CoV-2’s origin. They are remarkable the bat coronaviruses BANAL52 fromLaos and Rp22DB159 from Vietnam, which are the closest known relatives of SARS-CoV-2. Bat BANAL52 and Rp22DB159 spike glycorpotein havethe receptor binding domain almost identical to that of SARS-CoV-2, they can therefore infect human cells, despite the absence of the polybasic furin cleavage motif. Consistently, BANAL52 and Rp22DB159 sarbecoviruses have the characteristics to be considered progenitors of SARS-CoV-2. The key evolutionary step leading to the pandemic virus was the acquisition in a progenitor of SARS-CoV-2 the S gene insert encoding the polybasic furin cleavage site. Ahypothesis for the probable human origin of that S gene insertincludes that it has been acquired by recombination between the genome of a progenitor of SARS-CoV-2 and human mRNA transcripts within human infected cells. The question is whether it could be that in some cases this recombination did not occur. At this point, I was interested in conducting a sequenceanalysis to explore whether existSARS-CoV-2 isolatesmissing the furin cleavage motif. With the purpose of creating a curated working sample, I downloaded from NCBI Virus database SARS-CoV-2 spike glycoprotein sequences with the following filters: host, human; ambiguous characters, 0; sequence length, min. 1260, max. 1300. The total number of downloaded sequences was 2,331,196. As a results, 3,070 sequencesshowed specific mutations within the novel RRAR furin cleavage motif. However, here I show eightSARS-CoV-2 isolates missing part of the furin site including the RRAR cleavage motif. These eightSARS-CoV-2 isolates show the TMPRSS2 cleavage motif at the S1/S2 junction regionstrictly conserved. In conclusion, results suggest that as long as TMPRSS2 cleavage site would be present at the SARS‐CoV-2 spike glycoprotein S1/S2 junction, the furin clevage sitemay not be entirely essential. At least it is not for eight SARS-CoV-2 isolates.