The family of viruses that gave rise to COVID-19 has been circulating in horseshoe bats for decades, and this lineage includes other viruses with the ability to infect humans, according to a new study from Penn State.
An international team of researchers has traced the evolutionary history of SARS-CoV-2, and the findings may help to prevent future pandemics that could emerge from this lineage.
“Coronaviruses have genetic material that is highly recombinant, meaning different regions of the virus’s genome can be derived from multiple sources,” said study co-author Professor Maciej Boni. “This has made it difficult to reconstruct SARS-CoV-2’s origins.”
“You have to identify all the regions that have been recombining and trace their histories. To do that, we put together a diverse team with expertise in recombination, phylogenetic dating, virus sampling, and molecular and viral evolution.”
The team used three different approaches to identify and remove the recombinant regions within the SARS-CoV-2 genome. This enabled the experts to reconstruct and compare phylogenetic histories for the non-recombinant regions to pinpoint which viruses have been involved in recombination events in the past.
The study revealed the evolutionary relationships between SARS-CoV-2 and its closest known bat and pangolin viruses.
The family of viruses that includes SARS-CoV-2 was found to have diverged from other bat viruses about 40 to 70 years ago.
Bat coronavirus RaTG13 was sampled from a Rhinolophus affinis horseshoe bat in 2013 in Yunnan province, China. While SARS-CoV-2 shares about 96 percent of the genetic makeup of this particular virus, the researchers determined that it diverged from RaTG13 in 1969.
“The ability to estimate divergence times after disentangling recombination histories, which is something we developed in this collaboration, may lead to insights into the origins of many different viral pathogens,” said study co-author Philippe Lemey.
The analysis showed that one of the older traits SARS-CoV-2 shares with its relatives is the receptor-binding domain (RBD) located on the Spike protein, which enables the virus to detect and bind to receptors on human cells.
“This means that other viruses that are capable of infecting humans are circulating in horseshoe bats in China,” said study co-author David L. Robertson.
Furthermore, it has not been confirmed that the viruses will require an intermediate host to jump to humans. According to Robertson, for SARS-CoV-2, other research groups incorrectly proposed that key evolutionary changes occurred in pangolins.
“SARS-CoV-2’s RBD sequence has so far only been found in a few pangolin viruses,” said Robertson. “Furthermore, the other key feature thought to be instrumental to SARS-CoV-2’s ability to infect humans – a polybasic cleavage site insertion in the Spike protein – has not yet been seen in another close bat relative of the SARS-CoV-2 virus.”
“Yet, while it is possible that pangolins may have acted as an intermediate host facilitating transmission of SARS-CoV-2 to humans, no evidence exists to suggest that pangolin infection is a requirement for bat viruses to cross into humans.”
“Instead, our research suggests that SARS-CoV-2 likely evolved the ability to replicate in the upper respiratory tract of both humans and pangolins.”
The experts concluded that preventing future pandemics will require better sampling within wild bats. Prevention will also require the implementation of human disease surveillance systems that are able to instantly identify unknown pathogens.
“The key to successful surveillance, is knowing which viruses to look for and prioritizing those that can readily infect humans. We should have been better prepared for a second SARS virus,” said Robertson.
“We were too late in responding to the initial SARS-CoV-2 outbreak, but this will not be our last coronavirus pandemic,” said Professor Boni. “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.”
The study is published in the journal Nature Microbiology.