What do the humans, snow leopards, minks and white-tailed deer all have in common? They can all be infected by the SARS CoV-2 virus that currently has the world in the grip of a deadly pandemic.
Now, a team of scientists has drawn up a list of more than 500 other mammals that are likely candidates for catching and spreading the virus. Armed with detailed models of how the virus binds with a host’s cells and a computer program capable of teasing out common traits for that binding site among different species, researchers found potential viral targets spanning 13 biological orders, from tiny mice to hulking gorillas.
The findings could help pinpoint which among thousands of species should be monitored, as scientists work to reduce risks that the virus–and dangerous new viral mutants–will move back and forth between humans and other animals. “Knowing which mammals are capable of re-infecting us is vital to preventing spillback infections and dangerous new variants,” said Ilya Fischhoff, a postdoctoral researcher at the Cary Institute of Ecosystem Studies who helped lead the work.
Scientists have already pinpointed a handful of animal species that can swap the virus. The pandemic is suspected to have begun with such a jump, though it’s not known which species transmitted it to a person. Mink have been infected by people and then spread the disease back again. In the Midwest and East Coast of the U.S., 40% of white-tailed deer tested recently carried the virus. Each infected species provides a reservoir through which the virus can spread and mutate. As the delta and now the omicron variants show, new versions of the virus can upset efforts to control a disease that has already claimed more than 5.2 million people.
But knowing which animals are vulnerable to the virus isn’t straightforward. Attention has focused on the angiotensin-converting enzyme 2 (ACE2) receptor, a protein commonly found on the surface of mammalian cells that the SARS-CoV-2 virus binds to with a spike-like protein. The receptor is commonly involved in such basic bodily functions as regulating blood pressure. But for the virus it acts like a gateway to the cell’s inner workings.
To find potential candidates, scientists have looked for animals with a similar ACE2 receptor, based on the receptor’s building blocks of amino acids or three-dimensional models of how a specific receptor will interact with the virus’s spike protein. The problem is, the exact ACE2 structure is known for only around 300 species.
Scientists at the Cary Institute, a New York-based nonprofit research institute, along with scientists at Stanford and Arizona State University, turned to computers for a shortcut around the laborious and time-consuming effort of detailing every species’ ACE2. First, they collected the amino acid sequences for 326 species and plugged them into a computer program designed to simulate how well the virus’s spike protein would bind to it–like seeing how a key matches with a lock.
To weed out the animals whose ACE2 receptors were unlikely to have a strong enough bond, they set a threshold for a binding level between the animal with the weakest bond that has been shown to spread the disease–a domestic cat–and the species with the strongest bond that still doesn’t spread the disease–the domestic pig.
Then, they used a computer program to comb through databases of basic biological traits for 5400 mammals–everything from where it hunts for food to the body length of newborns–looking for patterns of characteristics that connected animals with known ACE2 sequences and a high likelihood of infection, to other less-studied species.
“It’s likely that it (the receptor) evolved in animals alongside other ecological and life history traits. By comparing biological traits of species known to have the ACE2 receptor with traits of other mammal species, we can make predictions about their capacity to transmit SARS-CoV-2,” said Adrian Castellanos, a Cary Institute postdoctoral researcher involved in the work.
The analysis highlighted 540 species as high-risk, according to results published in mid-November in the Proceedings of the Royal Society B. It names known SARS-CoV-2 carriers–deer mice, raccoon dogs, minks and white-tailed deer. It also included surprises such as the saola, also known as the “Asian unicorn,” a rare, jungle-dwelling creature that resembles a small antelope.
Among the most heavily represented types of animals are primates, sloths and anteaters, pangolins, treeshrews, bats and a bevy of grazing animals. A number of the top species live in close contact with people increasing the potential risk of an interspecies infection. The water buffalo is widely used for milk and plowing in parts of the world. Mink, red fox, sika deer and white-lipped peccary are all farmed. Macaque monkeys are kept as pets. People routinely hunt duikers, warty pigs and deer.
The results don’t guarantee a species will turn out to be a problem. For example, pigs ranked relatively high, but the virus didn’t infect them in lab experiments. However, the findings can help narrow down the list of likely suspects as disease detectives hunt for more potential carriers of the virus. “Our model is the only one that has been able to make risk predictions across nearly all mammal species,” said senior author and Cary Institute disease ecologist, Barbara Han. “Every time we hear about a new species being found SARS-CoV-2 positive, we revisit our list and find they are ranked high.”
Fischhoff, et. al. “Predicting the zoonotic capacity of mammals to transmit SARS-CoV-2.” Proceedings of the Royal Society B. Nov. 17. 2021.