Close relatives of virus that caused Covid-19 pandemic may have been circulating in bats for decades: Study
Researchers found that the lineage of viruses to which SARS-CoV-2 belongs diverged from other bat viruses about 40-70 years ago
Viruses closely related to SARS-CoV-2, which is responsible for the Covid-19 pandemic, may have been circulating unnoticed in bats for many decades, long before the virus started infecting people last year, according to a new study which sheds light on the origin of the viral strain behind the pandemic.
By reconstructing the evolutionary history of SARS-CoV-2, the virus that causes Covid-19, an international research team of Chinese, European and US scientists has discovered that the lineage of viruses to which SARS-CoV-2 belongs diverged from other bat viruses about 40-70 years ago, and likely includes different viruses with the ability to infect humans. The team estimates that SARS-CoV-2 genetically diverged from related bat sarbecoviruses in 1948, 1969, and 1982. The findings have implications for the prevention of future pandemics stemming from this lineage. “Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948, 1969, and 1982, indicating that the lineage giving rise to the virus has been circulating unnoticed in bats for decades,” write authors in the study published in Nature Microbiology.
The study also suggests that the Covid-19 virus may have jumped directly into humans from the horseshoe bats rather than via an intermediate host, suspected by many to be the pangolins. Commenting on the findings, Mark Pagel, professor of evolutionary biology at the University of Reading, who was not involved in the study, says: “The authors’ analyses, if correct, suggest that coronaviruses capable of infecting humans have been present in bats for perhaps 40 to 70 years but have gone undetected. This is significant in pointing to the scale and nature of the problems that zoonotic transmission presents to humans — there may be numerous and as yet undetected viruses capable of infecting humans that reside in animal hosts.”
The research team was able to reconstruct the evolutionary relationships between SARS-CoV-2 and its closest known bat and pangolin viruses. “Coronaviruses have genetic material that is highly recombinant, meaning different regions of the virus's genome can be derived from multiple sources. 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,” writes Maciej Boni, associate professor of biology, Penn State.
While the Covid-19 virus is genetically similar (about 96%) to the RaTG13 coronavirus, which was sampled from a Rhinolophus affinis horseshoe bat in 2013 in Yunnan province, China, the team found that it diverged from RaTG13 a relatively long time ago, 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,” says Philippe Lemey, principal investigator in the Department of Evolutionary and Computational Virology, KE Leuven.
The spike protein is the region of the Covid-19 virus that allows it to gain access to human cells and is the part of the virus that vaccine developers are targeting. 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 implies that other viruses that are capable of infecting humans are circulating in horseshoe bats in China. But are these viruses capable of jumping directly from bats into humans or will an intermediate species be required?
According to David L Robertson, professor of computational virology, MRC-University of Glasgow Centre for Virus Research, 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. Further, 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,” explains Robertson.
Professor Pagel says that the authors’ work is robust but unlikely to be the final word. “If they are correct, there will be coronaviruses circulating in horseshoe or other closely related bats that will prove to be closer to covid-19 than is RaTG13. In an earlier epidemic – that of the original SARS – researchers searched for over 14 years before finding the probable source, also in horseshoe bats,” adds Pagel.
According to the researchers, the findings underscore the need for a global network of real-time human disease surveillance systems that can identify novel pathogens in humans and respond in real-time, suggest experts. They say given what was known about the origins of SARS, as well as identification of SARS-like viruses circulating in bats that had binding sites adapted to human receptors, appropriate measures should have been in place for immediate control of outbreaks of novel coronaviruses.
The key to successful surveillance is knowing which viruses to look for and prioritizing those that can readily infect humans, emphasize the authors. “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,” adds Boni.