Studies on the Covid-19 virus produce 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 become infectious in humans. Amino acids are organic compounds that form proteins.

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

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

The lilac coronaviruses recently found in Asia share genetic similarities to the pandemic strain in key areas of the spike protein, the structure that punctuates the virus’s surface and helps it attach to human cells, suggesting that the ability to infect humans has 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 lead author of the study, which was published in February on the Virological.org discussion forum.

The change in amino acids 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 evaluated by colleagues and sent to a journal for publication.

He and colleagues analyzed nearly 183,000 pandemic virus genetic sequences for changes that could have helped adapt to humans. They identified a mutation that changed a single amino acid on the spike protein 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 mammals that eat ants that some scientists initially assumed could be an intermediary in transmitting the virus to humans.

It is unclear whether the mutation was in the virus when it first infected humans or whether other changes were needed 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 should now conduct an aggressive search for the origin of the pandemic virus wherever horseshoe bats are left, said Linfa Wang, a professor of emerging infectious diseases at the Duke-NUS School of Medicine in Singapore and lead 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 comes from bats.”

Some US officials and scientists have said that the possibility of the virus spreading 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 coronaviruses. He denies storing or conducting research on SARS-CoV-2 before the pandemic began and says he maintains the highest safety standards and that none of his employees have tested positive for the virus.

But some U.S. scientists and officials want the institute to share its safety records and raw data from all its research on both naturally occurring viruses and “gain-of-function” experiments in which scientists manipulate genetic viruses to see if the changes increase them infect or spread. The Trump administration claimed in January, without presenting any 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 professionals – said they considered a laboratory accident an extremely unlikely source of the pandemic. But team leader Peter Ben Embarek said last week that the lab hypothesis “is certainly not off the table” and acknowledged that the team lacked the information needed to make a full assessment. “We haven’t audited any of these labs, so we don’t really have hard facts or detailed data about the work done,” he said during a seminar organized by the National University of Singapore.

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

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

“Your computer would explode,” he said of the difference. “If all the best scientists worked for me for the rest of my life, I couldn’t create it.”

It would not have been easy to realize the mutation of the virus that Dr. Weger-Lucarelli and his colleagues found. “There is no literature, at least not published, that shows that this coronavirus site is very important for human infection,” said Dr. Weger-Lucarelli.

Dr. Garry of Tulane University School of Medicine said he believed that if Wuhan Institute scientists studied a naturally evolving virus that was able to infect humans, or one more similar to the pandemic strain than the virus. which they reported, would do so. they revealed this to a top scientific journal.

The newly discovered coronaviruses support the argument that “nature developed this virus without human intervention,” said Stanley Perlman, a University of Iowa virologist who has studied coronaviruses for four decades but has not been involved in recent studies. He is part of the Covid-19 Lancet commission set up to speed up pandemic solutions.

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

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

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

They have more powerful tools than during SARS research. These include a blood test that can speed up the search by quickly detecting neutralizing antibodies, which block the infection and last longer than the viral genetic material, said 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. The team also found a coronavirus that closely resembles the pandemic strain of 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 conserved samples of bat saliva and feces in Cambodia and Japan.

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

—Jeremy Page contributed to this article.

Write to Betsy McKay at [email protected]