The family of SARS-CoV-2, the virus responsible for the Covid-19 pandemic, has been lurking in the bat caves of China for decades and most likely includes other relatives that could infect humans. That’s according to a new study published in the journal Nature Microbiology this week.
An international team of scientists from the UK, Belgium, China, and the US traced the evolutionary history of SARS-CoV-2 by studying genetically related coronaviruses found in bats and pangolins. Understanding the evolutionary origins of the novel coronavirus can be fiddly as they undergo a process known as recombination, in which two different viruses both infect the same host cell and interact during replication, resulting in genetic material being swapped. This means their genome does not have a straight-forward lineage and can come from multiple sources.
According to the new findings, the lineage of viruses to which SARS-CoV-2 belongs to genetically is split between related bat coronaviruses that diverged in 1948, 1969, and 1982. One of these divergences, in 1969, eventually gave rise to RaTG13, a coronavirus that's 96.1 percent genetically similar to SARS-CoV-2. Researchers first identified this virus in 2013 after sampling a horseshoe bat in China’s Yunnan province.
Another key feature analyzed by the researchers was the receptor-binding domain (RBD) on the virus’ spike protein, an important part of the virus that's effectively the “key” used by the pathogen to recognize and enter host cells. The researchers found that SARS-CoV-2 and its relatives — such as RaTG13 and a pangolin virus sampled in Guangdong in 2019, Pangolin-2019 — all share a similar RBD and spike protein. However, these features do not appear to be the product of recombination. This suggests the protein and its RBD are an ancestral trait of the lineage leading to SARS-CoV-2, RaTG13, and Pangolin-2019.
It also hints that there could be other members of this family that are capable of infecting humans.
“This means that other viruses that are capable of infecting humans are circulating in horseshoe bats in China,” David L Robertson, study author and professor of computational virology at MRC-University of Glasgow Centre for Virus Research, explained in a statement.
The findings also throw doubt on the theory that pangolins, scaly-skinned mammals from Asia and Africa, were the intermediary animal that harbored the virus before it jumped to humans. Previous research suggested SARS-CoV-2’s RBD sequence was more similar to pangolin viruses than RaTG13. However, the team found there was no evidence that pangolins helped to arm SARS-CoV-2 with the RBD during its evolutionary history. Although pangolins may have played a role in the transmission to humans, they are unlikely to be the chief intermediate host for the virus.
The study also highlights a final damning question: if these potentially deadly viruses have been circulating in bats for decades, then why did the Covid-19 pandemic catch the world off guard? To protect against the next coronavirus pandemic, the study authors say their findings further highlight how the world must carry out more research and surveillance to identify novel pathogens.
“We were too late in responding to the initial SARS-CoV-2 outbreak, but this will not be our last coronavirus pandemic. A much more comprehensive and real-time surveillance system needs to be put in place to catch viruses like this when case numbers are still in the double digits,” added Maciej Boni, study author and associate professor of biology at Penn State University.