In the summer of 2020, half a year after the coronavirus epidemic, scientists traveled to the forests of northern Laos to catch bats that could harbor cousins close to the pathogen.
In the dark of night, they collect samples of saliva, urine and feces as the animals emerge from nearby caves using fog traps and canvas traps, then leave them in the dark again.
The excrement samples contained coronavirus, which scientists studied using special protective gear and air filters in a high-security biosecurity lab known as BSL-3.
Three of the coronaviruses in Laos were abnormal: they carried a molecular hook on their surface that resembled the hook of the virus that causes Covid-1, called SARS-Cov-2. Like SARS-CoV-2, their hooks allow them to be trapped in human cells.
“It’s better than the initial strain of SARS-COV-2,” said Mark Elliott, a virologist at the Pasteur Institute in Paris. The study was posted online last month and has not yet been published in a scientific journal.
Virus experts are buzzing about the discovery. Some suspect that viruses such as SARS-CoV-2 can already infect humans from time to time, resulting in only mild and limited outbreaks. But under the right circumstances, pathogens like Covid-1 can cause epidemics, they say.
Experts say the study also has significant implications for the alleged controversy over the origin of covid. Some people have speculated that the impressive ability of SARS-CoV-2 to infect human cells cannot be developed through an animal’s natural spillover. But new discoveries seem to suggest otherwise.
“It really puts to bed the idea that the virus was created, or somehow manipulated in a lab, to infect people,” said Michael Warobi, a virologist at the University of Arizona.
More than a dozen more bat virus discoveries made in Laos, Cambodia, China and Thailand in recent months could help researchers better predict future epidemics. The family tree of the virus indicates where potentially dangerous species are hiding and which animals scientists should look at to find them.
Last week, the U.S. government announced a 125 million project to identify thousands of wild viruses in Asia, Latin America and Africa to determine their spillover risk. Dr. Elliott predicted that many more relatives of SARS-Cove-2 remain to be found.
“I’m a fly fisherman,” he said. “Just because I can’t catch trout doesn’t mean there are no trout in the river.”
When SARS-CoV-2 first came to light, its closest known relative was a bat coronavirus that Chinese researchers found in 2016 in a mine in southern China’s Yunnan province. RaTG13, as it is known, shares 96 percent of its genome with SARS-CoV-2. Based on the mutations carried by each virus, scientists have speculated that RaTG13 and SARS-CoV-2 are common ancestors that infected bats about 40 years ago.
Both viruses infect the cells using a molecular hook, called a “receptor-binding domain”, that sticks to their surface. Ratji 13’s hook, adapted to attach to bat cells, can only be weakly grasped in human cells. The hook of SARS-CoV-2, in contrast, can trap cells in the human respiratory tract, the first step towards a potentially fatal case of Covid-1 of.
To find other close relatives of SARS-CoV-2, wildlife virus experts have tested their freezers filled with old samples around the world. They have identified several similar coronaviruses from southern China, Cambodia and Thailand. Most came from bats, while a few came from scale mammals known as pangolins. No one was closer than RTG13.
Dr. E. Elliott and his colleagues set out to find a new coronavirus instead.
They traveled to northern Laos, about 150 miles from the mine where Chinese researchers found RaTG13. In six months they caught 55 bats, of which 455 are different species. Bats harbored two dozen types of coronaviruses, three of which resembled SARS-COV-2 বিশেষ especially in the receptor-binding domain.
In RaTG13, 11 of the 17 main building blocks in the domain resemble SARS-CoV-2. But of the three viruses from Laos, 16 were the same – the closest match so far.
Dr. E. Elliott speculated that one or more coronaviruses may be able to infect humans and cause mild disease. In a separate study, he and colleagues took blood samples from people in Laos who collected bat guano for a living. Although Laotians have shown no signs of being infected by SARS-CoV-2, they carry immune signs, called antibodies, which are caused by a similar virus.
Lingfa Wang, a molecular virologist at Duke-NUS Medical School in Singapore who was not involved in the study, agreed that such an infection was possible, since the newly discovered viruses could be strongly linked to human cell proteins called ACE2.
“If the receptor binding domain ACE2 is ready to use, these guys are dangerous,” said Dr. W Wang.
Ironically, some of the three Laotian viruses are more closely related to SARS-CoV-2 than other gen viruses. The cause of this genetic patchwork is the complex evolution of the coronavirus.
If a bat infected with a coronavirus could catch a second, two different viruses could be killed in a single cell at once. As that cell begins to replicate each virus, their genes become random together, creating new virus hybrids.
In the Laotian coronavirus, this gene shuffling gave them a receptor-binding domain similar to that of SARS-CoV-2. According to a preliminary analysis of Spiros lytras, a graduate student at the University of Glasgow in Scotland, the original genetic swap occurred almost a decade ago.
Mr. Lytras and his colleagues are now comparing SARS-CoV-2 with other close relatives found in recent months, not with the new virus in Laos. They are finding more evidence of gene mutations. This process – known as recombination – can reshape viruses year after year.
“It’s becoming increasingly clear how important restructuring is,” he said. Said Litras.
He and his colleagues are now drawing random evolutionary plants of viruses like SARS-CoV-2 based on these new insights. Finding more viruses can help clear the picture. But scientists are divided over where to look for them.
Dr. E. Elliott believes the best bet is in a region of Southeast Asia where his colleagues found their coronavirus, as well as a mine near Yunnan where RaTG13 was found.
“I think the main landscape matches North Vietnam, northern Laos and southern China,” said Dr. E. Elliott.
The U.S. government’s new virus-hunting project, called DEEP VZN, could create one or more SARS-CoV-2-like viruses in that region. A spokesman for USAID, the agency financing the effort, named Vietnam as a country where researchers would investigate and said the new coronavirus was one of their top priorities.
Other scientists think it is worthwhile to look for relatives of SARS-CoV-2 farther away. Dr. Worwarobi of the University of Arizona said some bags of corona virus, such as SARS-CoV-2, have been found in eastern China and Thailand.
“Clearly the restructuring shows us that these viruses are part of a single gene pool across hundreds of miles if not thousands of miles,” said Dr. Wor Warobi.
Georgetown University biologist Colin Carlson suspects that a virus capable of creating an outbreak like Kovid may be hiding further away. Bats share many biological features with animals known to carry viruses, such as SARS-CoV-2, as far as Indonesia from the east and India in the west, he noted.
“It’s not just a Southeast Asian problem,” Dr. Carlson said. “These viruses are diverse, and they are more universal than we thought.”
The study of potentially dangerous viruses has renewed interest in the source of the epidemic by researchers using security measures. To win the DEEP VZN grant, scientists must provide a biosafety and biosafety plan, according to a USAID spokesperson, including staff training, field safety equipment guidelines and lab work safety measures.
If scientists find a closer cousin of SARS-CoV-2, it does not mean that they have created a deadly threat. These may fail to spread to humans, or some scientists speculate that they may be the cause of small outbreaks. Only seven coronaviruses are known to have jumped off the species barrier to become well-established human pathogens.
“There’s probably a wide range of other coronaviruses that don’t go anywhere,” said Jessica Metcalfe, an evolutionary ecologist at Princeton University.
Nevertheless, reconstitution may be able to turn a virus into a new threat somewhere. In May, researchers reported that two coronaviruses had been reunited in dogs in Indonesia. The result was a hybrid that infected eight children.
“When a coronavirus that we’ve been observing for decades, which we think could get our pets, jumps – we should have seen that coming, right?” Dr. Carlson Dr.