Covid-19 Virus Studies Provide New Clues on the Origin of Pandemic

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

Public health officials say it is critical to identify the origin of the pandemic to take steps to prevent future outbreaks, although it may take years to do so. This latest research contributes to evidence that the virus, called SARS-CoV-2, probably originated in bats and then naturally evolved to infect humans, possibly through an intermediary.

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

The coronaviruses of bats recently found in Asia share genetic similarities with the pandemic strain in key areas of the ear protein, the structure that stitches the surface of the virus and helps attach it to human cells, suggesting the ability to to infect humans naturally developed, according to one of the bat studies.

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

The change in amino acid also indicates a natural viral evolution, led James Weger-Lucarelli, a virologist at Virginia Tech, who led the study that identified the change in amino acids. It was placed on a preprint server, meaning it was not rated by peers, and was submitted to a journal for publication.

He and his colleagues analyzed nearly 183,000 genetic sequences of the pandemic virus for changes that might help adaptation in humans. They identified a mutation that altered a single amino acid on the vein protein and showed that it helps the virus infect and replicate human cells. 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 to transmit the virus to humans.

It is unclear whether the mutation was in the virus when it first infected humans, and whether other changes were needed to enable human transmission, Drs. Weger-Lucarelli said. “But we know that this particular amino acid is important for replication in human cells,” he said.

Scientists must now conduct an aggressive search for the origin of the pandemic virus, where horseshoe bats rest, says Linfa Wang, professor of emerging infectious diseases at Duke-NUS Medical School in Singapore and a senior author of one of the bat studies. These bats, which contain 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 is derived from bats.”

Some U.S. officials and scientists have said that the possibility that the virus started spreading as a result of a laboratory accident cannot be ruled out. The Wuhan Institute of Virology has a high-security laboratory facility that conducts research on bat coronaviruses. It denies that SARS-CoV-2 stored or conducted research before the pandemic began, saying it maintains the highest safety standards and that none of the staff tested positive for the virus.

But some scientists and U.S. officials want the institute to share its safety records and raw data on all of its naturally-occurring virus research, and experiments with ‘profit function’, in which scientists genetically manipulate viruses to see if the changes affect their ability 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 WTO team – an international group of biologists, epidemiologists and animal health specialists – said they considered a laboratory accident to be a highly unlikely source of the pandemic. But team leader Peter Ben Embarek said last week that the laboratory hypothesis “is definitely not off the table” and acknowledged that the team did not have the information necessary to make a full assessment. “We did not conduct an audit of any of these laboratories, so we do not really have facts or detailed data on the work done,” he said during a seminar organized by the National University of Singapore.

The WTO is expected to publish a summary report in the coming days on the team’s findings from its mission to Wuhan. A full report is not yet expected for a few weeks.

Chinese scientists reported shortly after the pandemic began that the Wuhan Institute of Virology has a virus whose genome corresponds to 96.2% of that of the Covid-19 virus. But the difference between the two viruses would have been too great for researchers to successfully develop the pandemic virus, said Dr. Wang said, who is an expert in viruses transmitted by bats.

“It’s going to explode your calculator,” he said of the difference. “If the best scientists had worked for me the rest of my life, I would not have been able to create it.”

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

Dr Garry of the Tulane University School of Medicine said he believes that if the scientists at the Wuhan Institute developed a virus naturally that could infect humans, or one that is more closely related to the pandemic strain than the virus they do reported it to a top scientific journal.

The newly discovered coronaviruses support the argument that ‘nature evolved this virus without any human intervention’, says Stanley Perlman, a virologist at the University of Iowa who has been studying coronaviruses for four decades but was not involved in the latest studies. He serves on the Lancet Covid-19 commission set up to expedite solutions to the pandemic.

Searching for the origin of an epidemic is painstaking work. It took an international research team nearly a decade to prove that bats were the likely source of the 2002 and 2003 epidemics of severe acute respiratory syndrome, or SARS, which killed nearly 8,100 people in 30 countries and killed 774 is.

They reported in 2013 that they found a coronavirus in bats that was very similar to the virus that causes SARS, with the ability to infect human cells.

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

They have more powerful tools than they had during the research on the origins of SARS. This includes a blood test that can speed up the search by quickly detecting neutralizing antibodies, which block infection and last longer than viral genetic material, says Dr. 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 said. The team also found a coronavirus that looks a lot like the pandemic strain in bats in a cave in eastern Thailand.

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

Earlier studies have also found close relatives of the new coronavirus in examples of bat saliva and dung in Cambodia and Japan.

Pangolins carry these coronaviruses, but were probably not involved in the origin of the pandemic, because none of the viruses isolated so far from them are close enough to SARS-CoV-2 to be the progenitor, said dr. Garry said.

—Jeremy Page contributed to this article.

Write to Betsy McKay by [email protected]