Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

SARS-CoV-2 and the Secret of the Furin Site

Version 1 : Received: 5 February 2021 / Approved: 10 February 2021 / Online: 10 February 2021 (15:46:12 CET)

How to cite: Romeu, A.R.; Ollé, E. SARS-CoV-2 and the Secret of the Furin Site. Preprints 2021, 2021020264. Romeu, A.R.; Ollé, E. SARS-CoV-2 and the Secret of the Furin Site. Preprints 2021, 2021020264.


The SARS-CoV-2 high infectivity is due to the functional polybasic furin cleavage site in the S protein. How it was acquired is unknown. There are two challenges to face: (i) an evolutionary model, to fit the origin of the coronavirus; and (ii) a molecular mechanism for the site acquisition. Here we show genomic fingerprints which are specific of Pangolin-CoVs, Bat-SARS-like (CoVZC45, CoVZXC21), bat RatG13 and human SARS-CoV-2 coronaviruses. This, along with phylogenetic analysis, we found that these species have the same evolutionary origin in the bat, including a genetic recombination of S gene between Pangolin-CoV (2017) and RatG13 ancestors. However, this does not explain why SARS-CoV-2 is the only of them with the furin site, which consists in four amino acid (PRRA) motif. The Arginine doublet is encoded by CGGCGG codons. Surprisingly, none of the Arginine doublet of other furin site of viral proteins from several type of viruses, are encoded by the CGGCGG codons. This makes it difficult to consider a virus recombination as mechanism for the PRRA acquisition. The origin of SARS-CoV-2, is the origin of the recognition cleavage site. The bat coronavirus RaTG13 appears to be the closest relative of the SARS-CoV-2, but was isolated in 2013. So, new RatG13 samples would provide insights into the acquisition of the polybasic motif.


SARS-CoV-2, RaTG13, Furin Site, Molecular Evolution, Bioinformatics.


Computer Science and Mathematics, Mathematical and Computational Biology

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