Researchers Identify Evolutionary Origins of SARS-CoV-2, First Emerged 40-70 Years Ago

“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 Philippe Lemey, principal investigator in the Department of Evolutionary and Computational Virology, KE Leuven.

The team found that one of the older traits that SARS-CoV-2 shares with its relatives is the receptor-binding domain (RBD) located on the Spike protein, which enables the virus to recognize and bind to receptors on 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 Centre for Virus Research.

Will these viruses be capable of jumping directly from bats into humans or will an intermediate species be required to make the leap? 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 team concluded that preventing future pandemics will require better sampling within wild bats and the implementation of human disease surveillance systems that are able to identify novel pathogens in humans and respond in real time.

“The key to successful surveillance,” said Robertson, “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.”

Boni added, “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.”

Support for this research was provided by the European Research Council, the Medical Research Council, the Research Foundation — Flanders and the National Natural Science Foundation of China.