The origin of SARS-CoV-2 has fueled a fierce debate. Although many virologists, and other members of the scientific community, assert that the most likely origin is an animal reservoir—namely bats—the lack of data on an animal reservoir has left holes that have been filled in by other (less likely) hypotheses.
Now, coronaviruses that are genetically similar to SARS-CoV-2 have been identified within bat populations. Such viruses were found to be circulating in cave bats living in the limestone karstic terrain in North Laos, within the Indochinese peninsula. The findings support the hypothesis that SARS-CoV-2 could have originated from bats living in the limestone caves of Southeast Asia and southern China.
This work is published in Nature, in the paper, “Bat coronaviruses related to SARS-CoV-2 and infectious for human cells.”
There have been previous reports of various SARS-CoV-2-related viruses in Asian Rhinolophus bats, including the closest virus from R. affniis, RaTG13, and in pangolins. However, the authors write that “SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 pathway have not yet been identified.”
The researchers tested 645 bats (belonging to six families and 46 species) living in the limestone caves in northern Laos. In doing so, they found three viruses that they considered to be closely related to SARS-CoV-2.
In addition, the genetic sequences encoding regions that bind to ACE2—the human cell receptor that SARS-CoV-2 uses to gain entry to cells—in the novel viruses were similar to that of SARS-CoV-2. This is particularly important because the spike sequence of the virus determines the binding affinity and is responsible for host range.
The bat viruses were able to bind to human ACE2 receptors more efficiently than the original SARS-CoV-2 strain isolated from humans. One of these viruses was also shown to replicate within human cell lines but was inhibited by antibodies neutralizing SARS-CoV-2.
In addition, the team found that the receptor binding domain (RBDs) of the spike proteins of these viruses differ from that of SARS-CoV-2 by only one or two residues at the interface with ACE2. Lastly, none of these bat viruses harbors a furin cleavage site in the spike.
The study supports the hypothesis that novel bat coronaviruses may have a potential for infecting humans similar to that of early strains of SARS-CoV-2, and is a key component to understanding the origin of the epidemics.