Study sheds more light on the evolutionary ancestry of SARS-CoV-2

There is an ongoing debate among policy makers and the general public about the origin of SARS-CoV-2, the virus that causes COVID-19. While the researchers consider bats to be the most likely natural hosts for SARS-CoV-2, the origins of the virus are still unclear.

May 10 in the newspaper. Current biology, the researchers describe a recently identified bat coronavirus that is the closest relative of SARS-CoV-2 in some regions of the genome and that contains amino acid insertions at the junction of the S1 and S2 subunits of the virus spike protein. similar to SAR -CoV-2.

While not a direct evolutionary precursor to SARS-CoV-2, this new virus, RmYN02, suggests that such seemingly unusual insertion events may naturally occur in coronavirus evolution, the researchers say.

Since the discovery of SARS-CoV-2 there have been a number of unfounded suggestions that the virus is of laboratory origin. In particular, insertion of S1 / S2 has been proposed to be highly unusual and perhaps indicative of laboratory manipulation. Our article shows very clearly that these events occur naturally in wildlife. This provides strong evidence against SARS-CoV-2 as a laboratory escape.“

Weifeng Shi, lead author of the study, director and professor of the Institute of Pathogen Biology, Shandong First Medical University

The researchers identified RmYN02 from an analysis of 227 bat samples collected in Yunnan Province, China, between May and October 2019.

“Since the discovery that bats were the reservoir for the SARS coronavirus in 2005, there has been a great deal of interest in bats as reservoir species of infectious diseases, particularly because they have a wide diversity of RNA viruses, including coronaviruses,” he says. Shi.

The RNA from the samples was sent for next-generation metagenomic sequencing in early January 2020, shortly after the discovery of SARS-CoV-2.

Across the genome, the closest relative to SARS-CoV-2 is another virus, called RaTG13, which was previously identified from bats in Yunnan province. But RmYN02, the virus recently discovered here, is even more closely related to SARS-CoV-2 in some parts of the genome, including the longest coding section of the genome called 1ab, where they share 97.2% of their RNA.

The researchers note that RmYN02 does not closely resemble SAR-CoV-2 in the region of the genome that encodes the key receptor-binding domain that binds to the human ACE2 receptor that SARS-CoV-2 uses to infect host cells. This means that it is not likely to infect human cells.

The key similarity between SARS-CoV-2 and RmYN02 is the finding that RmYN02 also contains amino acid insertions at the point where the two subunits of its spike protein meet. SARS-CoV-2 is characterized by an insert of four amino acids at the junction of S1 and S2; This insert is unique to the virus and has been present in all SARS-CoV-2 sequenced so far.

Insertions in RmYN02 are not the same as in SARS-CoV-2, indicating that they occurred through independent insertion events. But a similar insertion event that occurs in a virus identified in bats strongly suggests that these types of insertions are naturally occurring.

“Our findings suggest that these insertion events that initially appeared to be very unusual may, in fact, occur naturally in animal beta-coronaviruses,” says Shi.

“Our work sheds more light on the evolutionary ancestry of SARS-CoV-2,” he adds. “Neither RaTG13 nor RmYN02 are the direct ancestors of SARS-CoV-2, because there is still an evolutionary gap between these viruses. But our study strongly suggests that sampling of more wildlife species will reveal viruses that are even more related to SARS-CoV-2 and perhaps even its direct ancestors, which will tell us a lot about how this virus arose in humans. “