Zoonosis is any illness or infection that is naturally transmissible from animals to humans. The current novel coronavirus pandemic has been linked to bats as the host, and pangolins as a possible intermediate host. Reverse zoonosis, on the other hand, is when an infection jumps from humans to animals.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can easily infect humans and has spread across the globe, with more than 23.5 million confirmed cases to date.
Now, a new genomics study by University of California, Davis, California researchers identifies a large number of mammals that can potentially be infected by SARS-CoV-2 via their ACE2 proteins.
Horseshoe Bat (Rhinolophus sp.). Image Credit: Hugh Lansdown / Shutterstock
What is the ACE2 receptor site?
The angiotensin-converting-enzyme 2 is a protein found on the surface of many cell types, including the heart, lungs, blood vessels, liver, kidneys, and the gastrointestinal tract. Mostly, it is found in epithelial cells, which form the lining of certain tissues to provide a protective barrier.
The SARS-CoV-2 uses the spike-like protein on its surface to bind to the ACE2, forming a lock-and-key mechanism. When the virus binds to the cell, it now enters and infects the cell. Hence, ACE2 acts as a cellular gateway for the virus that causes COVID-19.
SARS-CoV-2 virus binding to ACE2 receptors on a human cell, the initial stage of SARS-CoV-2 infection. Image Credit: Kateryna Kon / Shutterstock
ACE2 in animal species
The SARS-CoV-2 pandemic first appeared in Wuhan City in China, when a cluster of cases of a mysterious pneumonia-like illness emerged. Most of the cases were tied to a seafood market in the city, which has been known to sell wild animals.
The new study, which was published in the journal Proceedings of the National Academy of Sciences (PNAS), may help identify intermediate hosts for the coronavirus and reduce the risk for future outbreaks.
To arrive at the study findings, the researchers utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to see the conservation of ACE2 and its potential to be used as a receptor for the novel coronavirus.
The team formulated a five-category binding score based on the conservation properties of 25 amino acids crucial for binding between ACE and the spike protein for SARS-CoV-2. This way, they can evaluate how many of these amino acids are found in the ACE2 protein of the different species.
The 18 species predicted as very high in terms of vulnerability to SARS-CoV-2 include Old-World primates and great apes with ACE2 proteins identical to human ACE2 across all 25 binding residues. The 28 animals with high propensity include whales, dolphins, rodents, deer, giant anteaters, and lemuriform primates.
About 57 species ranked medium in terms of propensity of their ACE2 to bind SARS-CoV-2 S, including domestic cats, Siberian tigers, lemurs, New-World primates, cattle, bison, goat, sheep, water buffalo, giraffe, and the Tibetan antelope.
Interestingly, all chiropterans or bats scored low, including the Chinese rufous horseshoe bat, from which a coronavirus related to SARS-CoV-2 was identified. Further, only 7.7 percent of primate species’ ACE2 scored low or very low, and 61 percent of rodent species scored low or very low. Fishes, reptiles, and amphibians scored low or very low.
Meanwhile, pangolins, which are widely thought to be the intermediate host of SARS-CoV-2 scored very low.
“We predict that species scoring as very high and high for the propensity of SARS-CoV-2 S binding to ACE2 will have a high probability of becoming infected by the virus and thus may be potential intermediate hosts for virus transmission,” the researchers wrote in the paper.
“We also predict that many species having a medium score have some risk of infection, and species scored as very low and low are less likely to be infected by SARS-CoV-2 via the ACE2 receptor,” the researchers added.
The research team believes that the study can open the door in studying more about animals and how they can be affected by SARS-CoV-2 amid the ongoing pandemic, which has already killed more than 807,000 people worldwide.
“The data provide an important starting point for identifying vulnerable and threatened animal populations at risk of SARS-CoV-2 infection. We hope it inspires practices that protect both animal and human health during the pandemic,” Harris Lewin, lead author for the study and a distinguished professor of evolution and ecology at UC Davis, said in a statement.
The research team has found that about 40 percent of the species potentially susceptible to SARS-CoV-2 are classified as “threatened” by the International Union for Conservation of Nature, and might be especially vulnerable to reverse zoonosis or human-to-animal transmission.