SARS-CoV-2′s claimed natural origin is undermined by issues with genome sequences of its relative strains Coronavirus sequences RaTG13, MP789 and RmYN02 raise multiple questions to be critically addressed by the scientific community

RaTG13, MP789, and RmYN02 are the strains closest to SARS-CoV-2, and their existence came to light only after the start of the pandemic. Their genomes have been used to support a natural origin of SARS-CoV-2 but after a close examination all of them exhibit several issues. We specifically address the presence in RmYN02 and closely related RacCSxxx strains of a claimed natural PAA/PVA amino acid insertion at the S1/S2 junction of their spike protein at the same position where the PRRA insertion in SARS-CoV-2 has created a polybasic furin cleavage site. We show that RmYN02/RacCSxxx instead of the claimed insertion carry a 6-nucleotide deletion in the region and that the 12-nucleotide insertion in SARS-CoV-2 remains unique among Sarbecoviruses. Also, our analysis of RaTG13 and RmYN02's metagenomic datasets found unexpected reads which could indicate possible contamination. Because of their importance to inferring SARS-CoV-2 ' s origin, we call for a careful reevaluation of RaTG13, MP789 and RmYN02 sequencing records and assembly methods.

Automated summary

RaTG13, MP789, and RmYN02 are strains closest to SARS-CoV-2, but a closer examination reveals issues such as a 6-nucleotide deletion in RmYN02 instead of claimed insertion and unexpected reads in metagenomic datasets. The unique 12-nucleotide insertion in SARS-CoV-2 suggests careful reevaluation of sequencing records and assembly methods for these strains.