Covid-19 virus studies provide new clues as to the origins 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 make the virus infectious in humans. Amino acids are organic compounds that form proteins.

Public health officials say it is critical to tracing the origins of the pandemic to take action to prevent future outbreaks, although it may take years to do so. These latest studies add to the evidence that the virus, called SARS-CoV-2, likely originated from 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 in February – the Chinese city where the first known cases of Covid-19 were found – are calling for a search for the origins of the pandemic in Wuhan. other countries besides China, especially those along the border in Southeast Asia.

The bat coronaviruses recently found in Asia have genetic similarities to the pandemic strain in key regions of the spike protein, the structure that covers the surface of the virus and helps it attach to human cells, suggesting the ability to treat humans to infect has evolved naturally, according to one of the bat studies.

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

The amino acid change also suggests natural viral evolution, said James Weger-Lucarelli, a Virginia Tech virologist who led the study that identified that amino acid change. It is posted on a preprint server, meaning it has not been peer-reviewed, and sent to a magazine for publication.

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

It’s unclear whether the mutation was in the virus when it first infected humans, or if other changes were needed to allow human transmission, said Dr. Weigher-Lucarelli. “But we know that this particular amino acid is important for replication in human cells,” he said.

Scientists should now aggressively search for the origins of the pandemic virus wherever horseshoe bats reside, said Linfa Wang, professor of emerging infectious diseases at Duke-NUS Medical School in Singapore and a senior author on 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 US officials and scientists have said the possibility that the virus began to spread as a result of a laboratory accident cannot be ruled out. The Wuhan Institute of Virology has a high-security laboratory facility that researches bat coronaviruses. It denies storing or researching SARS-CoV-2 before the pandemic started, saying it has the highest safety standards and that none of its staff tested positive for the virus.

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

Members of the WHO team – an international group of biologists, epidemiologists and animal health specialists – have said they view a laboratory accident as an extremely unlikely cause of the pandemic. But Peter Ben Embarek, the team leader, said last week that the laboratory hypothesis “is certainly not off the table,” acknowledging that the team lacked the information it needed to make a full assessment. “We haven’t checked any of these labs, so we don’t really have any hard facts or detailed data on the work done,” he said at a seminar hosted by the National University of Singapore.

WHO is expected to publish a summary report in the coming days on the team’s findings during its mission to Wuhan. A full report is not expected for a few 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% similar to 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, an expert in bat-borne viruses.

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

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

Dr. Garry of Tulane University School of Medicine said he believed that if scientists at the Wuhan Institute had studied a naturally evolved virus that could infect humans, or a virus more closely related to the pandemic strain than the virus they reported, they said that would have announced that to a top scientific journal.

The newly found coronaviruses support the argument that “nature evolved this virus without human intervention,” said Stanley Perlman, a University of Iowa virologist who has studied coronaviruses for four decades but was not involved in the latest studies. He is a member of the Lancet Covid-19 committee created to accelerate solutions to the pandemic.

Finding the origin of an epidemic is a laborious job. It took an international team of researchers nearly a decade to prove that bats were the likely source of the epidemic of severe acute respiratory syndrome, or SARS, in 2002 and 2003, which saw nearly 8,100 people sick in 30 countries, killing 774 people.

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 precursor virus – a strain that is more than 99% identical to the Covid-19 virus, but not as transmissible in humans. They are also looking for an ancestor virus from which the progenitor evolved.

They have more powerful tools than during the investigation into the origin of SARS. One is a blood test that can speed up the search by quickly detecting neutralizing antibodies, which block infections and last longer than viral genetic material, said Dr. Wang, who developed the test together 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. That likely means the animals were exposed to a coronavirus similar to the pandemic version, said Dr. Cheek. The team also found a coronavirus very similar to the pandemic strain of bats in a cave in eastern Thailand.

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

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

Pangolins carry these coronaviruses, but were likely not involved in the pandemic’s origins, because none of the viruses isolated so far are close enough to SARS-CoV-2 to be the progenitor, said Dr. Garry.

—Jeremy Page contributed to this article.

Write to Betsy McKay at [email protected]