Skip to main content

A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein

Our take —

Surveillance of coronaviruses in bats in southern China performed between May and October, 2019 revealed the presence of another virus closely related to SARS-CoV-2. Although the virus is still too genetically distant from SARS-CoV-2 to represent the direct source of human infections, the virus does possess insertions in the S1/S2 junction of the spike protein similar to SARS-CoV-2, thereby confirming that these insertions occur naturally. Additional surveillance of bats and other animals will likely discover additional close relatives of SARS-CoV-2.

Study design

Ecological; Other

Study population and setting

This study details the sequencing analysis of 302 skin, lung, liver, and feces samples collected from 227 bats of 20 species captured in Mengla County, Yunnan Province in southern China between May and October, 2019. The authors used a combination of metagenomic sequencing and PCR screening to detect coronaviruses in the collected bat samples.

Summary of Main Findings

One pool of 11 fecal samples collected from Rhinolophus malayanus bats between May 6 and July 30, 2019 produced two genome sequences for coronaviruses, one of which, RmYN02, was closely related to SARS-CoV-2. The genetic similarity between RmYN02 and SARS-CoV-2 across the whole genome was 93.3%, which is lower than the current closest relative, the bat coronavirus RaTG13. RmYN02 was the closest known relative to SARS-CoV-2 across the longest gene, ORF1ab, with a genetic similarity of 97.2%, but similarity within the spike gene and the receptor binding domain of the spike protein (which SARS-CoV-2 uses to enter host cells) was much lower in RmYN02 than in RaTG13. RmYN02 also displayed amino acid insertions between the S1 and S2 subunits of the spike protein, a unique feature that it shares with SARS-CoV-2 but had not yet been observed in bat coronaviruses. Modeling of the protein structure of the RmYN02 spike receptor binding domain showed important structural differences compared to SARS-CoV-2, so this virus potentially does not use ACE2 to enter bat host cells.

Study Strengths

The study benefits from a moderately large sample size of bats from multiple species in an area of China that is known to harbor a high diversity of SARS-related coronaviruses in bats. The sequencing methods used were appropriate for indicating the unique features of RmYN02 compared to SARS-CoV-2 and other viruses.

Limitations

Although RmYN02 does show important similarities with SARS-CoV-2, the virus is still quite distantly related to SARS-CoV-2 and does not represent the direct evolutionary progenitor of SARS-CoV-2. The supposed inability of RmYN02 to use the ACE2 receptor to enter host cells, as inferred from modeling the protein structure of the spike receptor binding domain, was not validated with experimental results (e.g., in bat cell lines).

Value added

The finding of amino acid insertions in the S1/S2 junction in a bat coronavirus, which had to date been unique to SARS-CoV-2, provides further evidence that SARS-CoV-2 is a virus of natural origin derived from viruses in bats.

This review was posted on: 4 July 2020