AUTHOR=Ambati Balamurali K. , Varshney Akhil , Lundstrom Kenneth , Palú Giorgio , Uhal Bruce D. , Uversky Vladimir N. , Brufsky Adam M. TITLE=MSH3 Homology and Potential Recombination Link to SARS-CoV-2 Furin Cleavage Site JOURNAL=Frontiers in Virology VOLUME=2 YEAR=2022 URL=https://www.frontiersin.org/journals/virology/articles/10.3389/fviro.2022.834808 DOI=10.3389/fviro.2022.834808 ISSN=2673-818X ABSTRACT=

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-CoV-2 genome encompassing the furin 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.