Coronavirus closely related to pandemic virus discovered in Japan and Cambodia

Two laboratory freezers in Asia have produced surprising discoveries. Researchers have said Nature have found a coronavirus that is closely related to SARS-CoV-2, the virus responsible for the pandemic, in horseshoe bats stored in a freezer in Cambodia. Meanwhile, a team in Japan reported the discovery of another closely related coronavirus, which is also found in the droppings of frozen bats.

The viruses are the first known relatives of SARS-CoV-2 to be found outside of China, supporting the World Health Organization’s search in Asia for the animal origin of the pandemic. Strong evidence suggests that SARS-CoV-2 originated in horseshoe bats, but whether it was transmitted directly from bats to people, or through an intermediate host, remains a mystery.

The virus in Cambodia was found in two Shamel’s horseshoe bats (Rhinolophus shameli) captured in the north of the country in 2010. The virus genome has not yet been fully sequenced, nor has its discovery been published, making it difficult to determine its full significance for the pandemic.

If the virus is closely related, or even an ancestor, to the pandemic virus, it could provide crucial information on how SARS-CoV-2 passed from bats to people and inform the search for the origin of the pandemic, says Veasna. Duong. virologist at the Pasteur Institute in Phnom Penh, who led the search for the ancient samples in Cambodia and alerted Nature upon its discovery in early November. To provide such insights, the virus would have to share more than 97% of its genome with SARS-CoV-2, which is more than its closest known relative, the researchers say.

But the new virus could have a more distant relationship, in which case studying it will help scientists learn more about the diversity in this family of viruses, says Etienne Simon-Loriere, a virologist at the Pasteur Institute in Paris, who plans to sequence the virus. . virus, after which it will be shared publicly.

This is the case with the other virus, called Rc-o319, identified in a small Japanese horseshoe bat (Rhinolophus cornutus) captured in 2013. This virus shares 81% of its genome with SARS-CoV-2, according to a document¹ released Nov. 2, making it too distant to provide information on the origin of the pandemic, says Edward Holmes, a virologist at the University of Sydney in Australia.

No matter what the Cambodian team finds, both discoveries are exciting because they confirm that viruses closely related to SARS-CoV-2 are relatively common in Rhinolophus bats, and even bats found outside of China, says Alice Latinne, an evolutionary biologist at the Wildlife Conservation Society Vietnam in Hanoi, who has seen some of the analysis by the Cambodian team but was not involved in the research.

“This is what we were looking for and we found it,” says Duong. “It was exciting and amazing at the same time.”

Origins of the pandemic

The findings also suggest that other as-yet-undiscovered SARS-CoV-2 relatives could be stored in laboratory freezers, says Aaron Irving, an infectious disease researcher at Zhejiang University in Hangzhou, China, who also plans to analyze stored samples of bats and bats. other mammals looking for antibodies to SARS-CoV-2.

“I did not expect to find a relative of SARS-CoV-2,” says virologist Shin Murakami of the University of Tokyo, who was part of the team that decided to retest frozen animal samples for viruses in the wake of the pandemic.

Only a handful of known coronaviruses are closely related to SARS-CoV-2, including its closest known relative RaTG13. It was discovered in intermediate horseshoe bats (Rhinolophus affinis) in China’s Yunnan Province in 2013, and published² only earlier this year. There are also several other coronaviruses, found in other Rhinolophus bats and pangolins captured between 2015 and 2019, which scientists now know are closely related to SARS-CoV-2.

“SARS-CoV-2 was probably not a new virus that appeared suddenly. Viruses in this group existed before we realized them in 2019, ”says Tracey Goldstein, associate director of the One Health Institute at the University of California at Davis, who is involved with the Cambodia team.

Latinne says the findings confirm that Rhinolophus bats are the reservoir for these viruses.

Cambodia virus

Duong’s team captured Shamel’s horseshoe bats in Cambodia as part of the US government-funded PREDICT project, which screened wildlife around the world for viruses with pandemic potential over decades and ended earlier this year. year. In April, the United States Agency for International Development awarded the program an additional $ 3 million and a 6-month extension to search for evidence of SARS-CoV-2 in samples from animals, primarily bats, as well as pangolins and other animals. , which were sat in laboratory freezers in Laos, Malaysia, Nepal, Thailand, Vietnam, and Cambodia. A full report of these investigations is expected in the coming weeks.

Duong says that preliminary genome sequencing of a short fragment of the novel bat virus (324 base pairs long) showed that it was similar to the same region in SARS-CoV-2 and RaTG-13, suggesting that all three they are closely related. That region is highly conserved in coronavirus, says Latinne, and is often used to quickly identify whether a virus is new or known. But it is not yet clear whether RaTG-13 or the new virus are more closely related to SARS-CoV-2.

It’s hard to tell with such a small fragment, says Vibol Hul, a virologist also at the Pasteur Institute in Cambodia, who caught Shamel’s horseshoe bats at a cave entrance in 2010. The genomes of most known coronaviruses contain about 30,000 bases. pairs.

In a separate analysis, the Cambodian team sequenced about 70% of the new virus genome using locally available technology, says Erik Karlsson, a virologist at the Pasteur Institute in Cambodia, who helped analyze the bats. In that sequence the instructions for crucial parts of the virus were missing, such as the genes that encode the spike protein that coronaviruses often use to enter cells. Sequencing that section will indicate whether this virus can infect human cells, Duong says.

The new virus would have to be at least 99% similar to SARS-CoV-2 to be an immediate ancestor of the current pandemic virus, Irving says. The genomes of RaTG13 and SARS-CoV-2 differ only by 4%, but this divergence represents between 40 and 70 years of evolution since they shared a common ancestor. Although decades apart, viruses are similar enough to use the same receptor to enter cells. Cellular studies suggest that RaTG13 could infect people.

Another close relative

Of the known coronaviruses related to SARS-CoV-2, the newly discovered Rc-o319 appears to be the most distant, Duong says.

In cell studies, the team from Japan found that the virus cannot bind to the receptor that SARS-CoV-2 uses to enter human cells, suggesting that it cannot easily infect people.

Shin says his colleagues captured more bats in Japan earlier this year and plan to test them for coronavirus. And in October, Hul returned to the cave in northern Cambodia to catch more bats.

There are probably more coronaviruses related to SARS-CoV-2 in Rhinolophus Bat populations, which live throughout the region, Holmes says. “Hopefully one or more of these will be so closely related to SARS-CoV-2 that we can consider it to be the true ancestor.”