Researchers Identify Evolutionary Origins of SARS-CoV-2

Reconstructing the evolutionary history of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, an international research team of Chinese, European, and American scientists discovered that the lineage that gave rise to the virus has been circulating in bats for decades and probably includes other viruses with the ability to infect humans. The findings, to which scientists from the University of Glasgow contributed, have implications for the prevention of future pandemics stemming from this lineage.

“Coronaviruses have genetic material that is highly recombinant, which means that different regions of the virus genome can be derived from multiple sources,” said Maciej Boni, associate professor of biology, Penn State. “This has made it difficult to reconstruct the origins of SARS-CoV-2. You must identify all the regions that have been recombining and trace their histories. To this end, we assembled a diverse team with expertise in recombination, phylogenetic dating, virus sampling, and evolution. molecular and viral. “

The team used three different bioinformatic approaches to identify and eliminate recombinant regions within the SARS-CoV-2 genome. They then reconstructed the phylogenetic histories of the non-recombinant regions and compared them to each other to see which specific viruses have been involved in recombination events in the past. They were able to reconstruct the evolutionary relationships between SARS-CoV-2 and its best-known bat and pangolin viruses. Their findings appear today in Microbiology nature.

The researchers discovered that the virus lineage to which SARS-CoV-2 belongs diverged from other bat viruses about 40-70 years ago. Importantly, although SARS-CoV-2 is genetically similar (about 96%) to the RaTG13 coronavirus, which was taken from a sample of a horseshoe bat Rhinolophus affinis in 2013 in Yunnan Province, China, the team found that it diverged from RaTG13 for a relatively long time ago, in 1969.

“The ability to estimate divergence times after unraveling recombination histories, which is something we developed in this collaboration, can lead to an understanding of the origins of many different viral pathogens,” said Philippe Lemey, principal investigator, Department of Evolutionary and Computational Virology, KE Leuven.

The team discovered that one of the oldest traits that SARS-CoV-2 shares with its relatives is the receptor binding domain (RBD) located on the Spike protein, which allows the virus to recognize and bind to receptors in the surfaces of human cells. .

“This means that other viruses that are capable of infecting humans are circulating in horseshoe bats in China,” said David L. Robertson, professor of computational virology, MRC University of Glasgow Virus Research Center.

Will these viruses be able to jump directly from bats to humans, or will an intermediate species be required to make the jump? According to Robertson, for SARS-CoV-2, other research groups incorrectly proposed that key evolutionary changes occurred in pangolins.

“The RBD sequence of SARS-CoV-2 has so far only been found in a few pangolin viruses,” said Robertson. Furthermore, the other key feature believed to be instrumental in the ability of SARS-CoV-2 to infect humans, an insertion of the polybasic cleavage site in the Spike protein, has yet to be seen in another close relative of the However, although pangolins may have acted as an intermediate host facilitating the transmission of SARS-CoV-2 to humans, there is no evidence to suggest that pangolin infection is a requirement for that bat viruses pass into humans. suggests that SARS-CoV-2 probably evolved the ability to replicate in the upper respiratory tract of both humans and pangolins. “

The team concluded that preventing future pandemics will require better sampling within wild bats and the implementation of human disease surveillance systems that can identify new pathogens in humans and respond in real time.

“The key to successful surveillance,” said Robertson, “is knowing what viruses to look for and prioritizing those that can easily infect humans. We should have been better prepared for a second SARS virus.”

Boni added: “It took us too long to respond to the initial SARS-CoV-2 outbreak, but this will not be our last coronavirus pandemic. A much more comprehensive, real-time surveillance system is needed to detect viruses like this when numbers of case are still in the double digits. ”