Covid-19 virus studies provide new clues about the origin of the pandemic

Another new study suggests that a change in a single amino acid in a key component of the virus allowed or at least helped the virus to become infectious in humans. Amino acids are organic compounds that form proteins.

Public health officials say it is critical to identify the source of the pandemic in order to take steps to prevent future outbreaks, although it may take years to do so. These latest research adds evidence that the virus, called SARS-CoV-2, probably originated from bats and evolved naturally to infect humans, possibly through an intermediate animal.

The studies also help to explain why members of a WHO team that completed a four-week mission in February in Wuhan, the Chinese city where the first known cases of Covid-19 were found, support the search for the origin of the pandemic in other countries in addition to China, especially those along its border with Southeast Asia.

Bat coronaviruses recently found across Asia share genetic similarities with the pandemic strain in key areas of the protein spike, the structure that dots the virus’s surface and helps it connect to human cells, suggesting that the ability to infect humans evolved naturally, according to one of the bat studies.

“All of these viruses come from nature,” said Robert Garry, a virologist at Tulane University School of Medicine and senior author of that study, which was published in February on the Virological.org discussion forum.

The amino acid change also suggests a natural viral evolution, said James Weger-Lucarelli, a Virginia Tech virologist who led the study that identified this amino acid change. It was posted on a prepress server, which means it was not peer-reviewed and sent to a newspaper for publication.

He and his colleagues analyzed some 183,000 genetic sequences of the pandemic virus for changes that may have helped adapt to humans. They identified a mutation that altered a single amino acid in the protein spike and showed that it helped the virus infect human cells and replicate. The amino acid was different in a related coronavirus that infects bats and pangolins, scaly ant-eating mammals that some scientists initially assumed could be an intermediary in transmitting the virus to humans.

It is not clear whether the mutation was in the virus when it first infected people, or whether other changes were necessary to allow human transmission, said Dr. Weger-Lucarelli. “But we know that this particular amino acid is important for replication in human cells,” he said.

Scientists must now aggressively search for the origin of the pandemic virus wherever horseshoe bats perch, said Linfa Wang, professor of emerging infectious diseases at Duke-NUS Medical School in Singapore and senior author of one of the bat studies. These bats, which carry coronaviruses, are found in tropical and temperate regions of Asia, the Middle East, Africa and Europe, he said, adding, “I am convinced that the ancestral virus came from bats.”

Some American officials and scientists said that the possibility that the virus started to spread as a result of a laboratory accident cannot be ruled out. The Wuhan Institute of Virology has a high security laboratory that conducts research on bat coronavirus. She denies storing or doing research on SARS-CoV-2 before the start of the pandemic and says she maintains the highest safety standards and that none of her employees tested positive for the virus.

But some scientists and U.S. officials want the institute to share its safety records and raw data in all of its research on naturally evolved viruses and “function gain” experiments in which scientists genetically manipulate viruses to see if changes increase their capacity to infect or spread. The Trump administration claimed in January, without providing evidence, that the institute had been conducting secret research for the Chinese military since 2017. Beijing said it “was not based on science or facts”.

Members of the WHO team – an international group of biologists, epidemiologists and animal health experts – said they considered a laboratory accident to be an extremely unlikely source of a pandemic. But Peter Ben Embarek, the team leader, said last week that the laboratory hypothesis “is definitely not out of the question” and acknowledged that the team did not have the information it needed to make a thorough assessment. “We have not audited any of these laboratories, so we have no hard facts or detailed data on the work done,” he said during a seminar organized by the National University of Singapore.

WHO is due to publish a summary report in the coming days on the team’s findings in its mission in Wuhan. A full report is not expected in the coming weeks.

Chinese scientists reported shortly after the start of the pandemic that the Wuhan Institute of Virology had a virus whose genome is 96.2% compatible with that of the Covid-19 virus. But the difference between the two viruses would have been too great for researchers to successfully create the pandemic virus, said Wang, who specializes in bat-borne viruses.

“It would blow up your calculator,” he said of the difference. “If all the best scientists worked for me for the rest of my life, I wouldn’t be able to create it.”

Nor would it have been easy to discover the mutation in the virus that Dr. Weger-Lucarelli and his colleagues found. “There is no literature, at least no one has published, showing that this location in coronaviruses is very important for human infection,” said Dr. Weger-Lucarelli.

Dr. Garry, of the Tulane University School of Medicine, said he believed that if scientists at the Wuhan Institute were studying a naturally evolved virus that was capable of infecting humans, or a virus more like the pandemic strain than the virus that reported, they would disclose this to an important scientific journal.

The newly discovered coronaviruses support the argument that “nature developed this virus without requiring any human intervention,” said Stanley Perlman, a virologist at the University of Iowa who has studied coronavirus for four decades but was not involved in the most recent studies. He serves on the Lancet Covid-19 Commission created to accelerate solutions to the pandemic.

Tracing the origin of an epidemic is hard work. An international team of researchers took nearly a decade to prove that bats were the likely source of the 2002 and 2003 severe acute respiratory syndrome epidemic, or SARS, which sickened some 8,100 people in 30 countries, killing 774.

They reported in 2013 that they had found a coronavirus in bats that looked very much like the virus that causes SARS, with the ability to infect human cells.

In their search now, scientists intend to find a parent virus – a strain that is more than 99% identical to the Covid-19 virus, but not transmissible in humans. They are also looking for an ancestral virus from which the parent evolved.

They have more powerful tools than when researching the origin of SARS. Among them is a blood test that can speed up research by quickly detecting neutralizing antibodies, which block the infection and last longer than viral genetic material, said Wang, who developed the test with his team.

Using the test, he and a team of researchers found strong neutralizing antibodies that blocked SARS-CoV-2 in bats and a pangolin in Thailand. This probably means that the animals were exposed to a coronavirus similar to the pandemic version, said Dr. Wang. The team also found a coronavirus very similar to the pandemic strain in bats in a cave in eastern Thailand.

The research was published in the journal Nature Communications in February.

Previous studies have also found close relatives of the new coronavirus in preserved samples of saliva and bat feces in Cambodia and Japan.

Pangolins carry these coronaviruses, but they were probably not involved in the origin of the pandemic because none of the viruses isolated from them until now are close enough to SARS-CoV-2 to have been the parent, said Dr. Garry.

—Jeremy Page contributed to this article.

Write to Betsy McKay at [email protected]