Chinese horseshoe bat is natural host to coronaviruses causing Covid-19 and SARS in 'evolutionary arms race'
Chinese virologist Dr Zheng-Li Shi, whose research made her a target of unsubstantiated theories that the new coronavirus escaped from a lab at the Wuhan Institute of Virology, has published new findings that look at how severe acute respiratory syndrome (SARS)-related pathogens have adapted to suit human hosts.
The study boosts the idea that the Chinese horseshoe bat is a natural host of coronaviruses like the ones that cause SARS and Covid-19, says the research team. Based on their findings, the researchers recommend that continued surveillance of this group of viruses in bats is necessary for the prevention of the next SARS-like disease.
The research explores the “evolutionary arms race” between viruses and their hosts, which the team says encourages genetic diversity in viruses. It says bats carried many coronaviruses with a high degree of genetic diversity, particularly in the spike protein, which suggested they had evolved to help their transmission.
“The Chinese horseshoe bat (Rhinolophus sinicus), reservoir host of severe acute respiratory syndrome coronavirus (SARS-CoV), carries many bat SARS-related CoVs (SARSr-CoVs) with high genetic diversity, particularly in the spike gene. Despite these variations, some bat SARSr-CoVs can utilize the orthologs of human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), for entry,” says the study, a pre-print version of which has been published. This implies that the study is yet to be peer-reviewed.
In the search for treatments for Covid-19, many researchers are focusing their attention on a specific protein that allows the virus to infect and destroy human cells. Called the angiotensin-converting enzyme 2, or ACE2 “receptor,” the protein provides the entry point for the coronavirus to hook into and infect a wide range of human cells.
According to the current study, SARS-related coronaviruses have co-evolved with its natural host, R. sinicus, for a very long time. “All tested bat SARSr-CoV spike proteins had a higher binding affinity to human ACE2 than to bat ACE2, although they showed a 10-fold lower binding affinity to human ACE2 compared with their SARS-CoV counterpart. Structure modeling revealed that the difference in binding affinity between spike and ACE2 might be caused by the alteration of some key residues in the interface of these two molecules,” says the research team in their findings.
They explain, “Molecular evolution analysis indicates that these residues were under strong positive selection. These results suggest that the SARSr-CoV spike protein and R. sinicus ACE2 may have co-evolved over time and experienced selection pressure from each other, triggering the evolutionary arms race dynamics. It further proves that R sinicus is the natural host of SARSr-CoVs.”
There is ongoing debate among policymakers and the general public about where SARS-CoV-2, the virus that causes Covid-19, came from. While researchers consider bats the most likely natural hosts for SARS-CoV-2, the origins of the virus are still unclear.
SARS-like coronavirus in Chinese horseshoe bats
In 2013, 10 years after the SARS outbreak, scientists discovered a new SARS-like coronavirus in Chinese horseshoe bats. In late 2002, a SARS epidemic broke out in southern China, ultimately killing hundreds of people in dozens of countries by the summer of 2003.
The international group of collaborators, which also included Dr Shi, uncovered genome sequences of a new virus closely related to the SARS coronavirus. The group was able to isolate the live SARS-like virus from bats allowing scientists to conduct detailed studies to create control measures to thwart outbreaks and provide opportunities for vaccine development. The research team isolated and cultured a live virus that binds to the human SARS receptor ACE2 and can, therefore, be transmitted directly from bats to people. They found plausible evidence that bats may directly infect humans.
During the original outbreak of SARS in the wet markets of Guangdong province in China, it was thought that bat viruses first infected civets, and then the virus evolved to infect people by this intermediate wildlife host. This study suggested that SARS may have originated from one of these viruses, precluding civets from playing a part in the transmission process. The paper does “provide compelling evidence that an intermediate host was not necessary,” said the research team in their findings published in Nature, adding that the findings highlight the necessity of preparedness for future emergence of SARS-like diseases. “The results point out the importance of continuing surveillance of viruses in bats, with the goals of identifying other viruses, including coronaviruses, that could cross species and potentially cause serious disease in humans or domesticated animals,” said the team.
Shi also published a paper in November 2017, which found that “genetic recombination between viral strains in bats” may have produced the "direct evolutionary ancestor" of the strain that caused a deadly outbreak of SARS in humans. In the study, researchers identified 11 new strains of the SARS virus and sequenced their full genomes to uncover their evolutionary relationships.
Genome analysis revealed that the newly-identified bat strains, as well as several strains identified in a previous study of the same bat cave, contained all the essential genetic building blocks of the human SARS coronavirus. Besides, the study also revealed that various SARS-related coronaviruses, capable of using human ACE2, are still circulating among bats in this region. Accordingly, the risk of spillover into people and the emergence of a disease similar to SARS is possible, the researchers concluded.