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Monday, February 21, 2022

COMPLEMENTARIEDAD HOMOLOGA DE SARS-CoV-2 y SECUENCIA PATENTADA DE mRNA (II)

COMPLEMENTARIEDAD HOMOLOGA DE SARS-CoV-2 y SECUENCIA PATENTADA DE mRNA (II) 

 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. 

 Keywords: SARS-CoV-2 spike, furin cleavage site, MSH3 gene, sequence homology, recombinability 

 FIGURE 1 | The origin of the furin sequence in SARS-CoV-2. Comparison of the protein sequences at the S1/S2 junction in SARS-CoV, RaTG13, and SARS-CoV-2 demonstrating the presence of the furin cleavage site (FCS) PRRA only in SARS-CoV-2. Based on a BLAST search of the 12-nucleotide stretch coding for the FCS PRRA, a 19-nucleotide long identical sequence was identified in the patented (US 958 7003) sequence Seq ID11652. SEQ ID11652 is transcribed to a MSH3 mRNA that appears to be codon optimized for humans. This 19-nucleotide sequence including 12 nucleotides coding for the FCS PRRA, present in the human MSH3 gene might have been introduced into the SARS-CoV-2 genome by the illustrated copy choice recombination mechanism in SARS-CoV-2 infected human cells overexpressing the MSH3 gene.



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