Coronavirus closely linked to pandemic virus discovered in Japan and Cambodia

Two laboratory freezers in Asia gave rise to surprising discoveries. The researchers said Nature they found a coronavirus closely linked to SARS-CoV-2, the virus responsible for the pandemic, in horseshoe bats stored in a freezer in Cambodia. Meanwhile, a team in Japan has reported the discovery of another closely related coronavirus – also found in frozen bat droppings.

Viruses are the first known relatives of SARS-CoV-2 to be found outside of China, supporting World Health Organization research across Asia to determine 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 humans, 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’s genome has not yet been fully sequenced – nor its discovery published – making its full significance for the pandemic difficult to determine.

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

But the new virus could be further away, in which case its study will help scientists learn more about the diversity of this family of viruses, explains Etienne Simon-Lorière, a virologist at the Institut Pasteur 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 (Rhinolophus cornutus) captured in 2013. This virus shares 81% of its genome with SARS-CoV-2, according to an article¹ published Nov 2 – making it too distant to give any insight into the origin of the pandemic, says Edward Holmes, a virologist at the University of Sydney in Australia.

No matter what the Cambodian team finds, the two findings are exciting as 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 Wildlife Conservation Society Vietnam in Hanoi, who saw part of the Cambodian team’s analysis but didn’t was not involved in the investigation.

“This is what we were looking for and we found it,” says Duong. “It was both exciting and surprising.”

Origins of the pandemic

The results also suggest that other as yet unknown relatives of SARS-CoV-2 could be stored in lab freezers, says Aaron Irving, an infectious disease researcher at Zhejiang University in Hangzhou, China, who also plans to test stored samples of bats and the like. mammals for antibodies against SARS-CoV-2.

“I didn’t 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 animal samples. frozen for viruses as a result 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 Yunnan Province of China in 2013, and was released² only earlier this year. There are also several other coronaviruses, found in others Rhinolophus bats and pangolins captured between 2015 and 2019, which scientists now know to be closely linked to SARS-CoV-2.

“SARS-CoV-2 was probably not a brand new virus that came on suddenly. The viruses in this group existed before we learned about them in 2019, ”says Tracey Goldstein, associate director of the One Health Institute at the University of California at Davis, who is involved in the Cambodian team.

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

Virus in Cambodia

Duong’s team captured Shamel’s horseshoe bats in Cambodia as part of the US government-funded PREDICT project, which has studied wildlife around the world for viruses with pandemic potential for decades. decades and ended earlier this year. In April, the U.S. Agency for International Development granted the program an additional $ 3 million and a 6-month extension to search for evidence of SARS-CoV-2 in animal samples – mostly bats, as well. than pangolins and other animals – who sat in lab 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 new bat virus – 324 base pairs long – has shown it to be similar to the same region in SARS-CoV-2 and RaTG- 13, suggesting that the three are closely related. This region is highly conserved in coronaviruses, says Latinne, and is often used to quickly identify whether a virus is new or known. But it’s not yet clear whether RaTG-13 or the new virus is more closely related to SARS-CoV-2.

It’s hard to tell with such a small fragment, says Vibol Hul, also a virologist at the Institut Pasteur in Cambodia, who trapped Shamel’s horseshoe bats at the entrance to a cave in 2010. The best-known coronavirus genomes contain about 30,000 bases. pairs.

In a separate analysis, the Cambodia team sequenced around 70% of the new virus’s genome using locally available technology, says Erik Karlsson, a virologist at the Institut Pasteur in Cambodia, who helped analyze bats. Instructions for crucial parts of the virus, such as the genes encoding the spike protein that coronaviruses typically use to enter cells, were missing in this sequence. The sequencing of this 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 share a common ancestor. Although separated by decades, viruses are similar enough to use the same receptor to enter cells. Cellular studies suggest that RaTG13 could infect people.

Another close relative

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

In studies on cells, the Japanese team found that the virus could not bind to the receptor used by SARS-CoV-2 to enter human cells, suggesting that it could not easily infect human cells. people.

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

There are likely more coronaviruses linked to SARS-CoV-2 Rhinolophus bat populations, which live in the area, says Holmes. “I hope that one or more of them will be so closely linked to SARS-CoV-2 that we can consider him to be the true ancestor.