MSH3 Homology and Potential Recombination Link to SARS-CoV-2 Furin Cleavage Site

• Published in: Frontiers in virology (online) 2022-02, Vol.2
• Main Authors: Ambati, Balamurali K, Varshney, Akhil, Lundstrom, Kenneth, Palú, Giorgio, Uhal, Bruce D, Uversky, Vladimir N, Brufsky, Adam M
• Format: Article
• Language: English
• Subjects: furin cleavage site; MSH3 gene; recombinability; SARS-CoV-2 spike; sequence homology
• ISSN: 2673-818X; 2673-818X
• DOI: 10.3389/fviro.2022.834808

Among numerous point mutation differences between the SARS-CoV-2 and the bat RaTG13 coronavirus, only the 12-nucleotide furin cleavage site (FCS) exceeds 3 nucleotides. A BLAST search revealed that a 19 nucleotide portion of the SARS.Cov2 genome encompassing the furing cleavage site is a 100% complementary match to a codon-optimized proprietary sequence that is the reverse complement of the human mutS homolog (MSH3). The reverse complement sequence present in SARS-CoV-2 may occur randomly but other possibilities must be considered. Recombination in an intermediate host is an unlikely explanation. Single stranded RNA viruses such as SARS-CoV-2 utilize negative strand RNA templates in infected cells, which might lead through copy choice recombination with a negative sense SARS-CoV-2 RNA to the integration of the MSH3 negative strand, including the FCS, into the viral genome. In any case, the presence of the 19-nucleotide long RNA sequence including the FCS with 100% identity to the reverse complement of the MSH3 mRNA is highly unusual and requires further investigations.