IN THE FIELD From epidemiology, an “spillover” is a virus that has jumped from one host species to another. The fallout of most concern to humans is that of other animals on Homo sapiens. These can then create “zoonotic” human diseases, of which covid-19 is thought to be a part (the original host of SARSVSoV-2 would be a species of bat still undetermined).

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However, such traffic can be carried out in both directions. For example, in 2020, the World Health Organization reported that SARSVSoV-2 had spread in Denmark from humans to farmed mink, and then spread from animal to animal to create a distinct veterinary epidemic. And, earlier this month, an article posted on BioRxiv, an electronic host for work that has yet to be peer reviewed, presented evidence that the virus also circulates in white-tailed deer in North America, presumably having overwhelmed people there. This all adds up to reports suggesting that pets, especially cats and dogs, may also pick up SARSVSoV-2-and in the case of cats at least, can then transmit it to others of their species.

The fallout of this type is potentially serious for two reasons. The first is that they create viral reservoirs beyond the easy reach of medical science and surveillance. Even if there are no human cases of covid in an area, such animal reservoirs mean that SARSVSoV-2 can still hide, waiting to spill out into people. The other is that exposure to the immune system of new hosts can lead to the evolution of new and (if they then reverberate) potentially threatening strains of the virus. The mink incident therefore led the governments of Denmark, the Netherlands and Spain to slaughter 18 million animals and impose strict closures in the areas around the affected fur farms. Treating a wild population, such as white-tailed deer, in the same way would be more difficult. But precautions are still possible. Educating those who interact with deer, such as hunters, can go a long way.

These are, however, reactive approaches. A proactive approach would try to establish which species are most at risk of becoming reservoirs for SARSVSoV-2 before they actually do. This would allow threats to be monitored before they get out of hand. And, as she reports this week in the Acts of the Royal Society, Barbara Han of the Cary Institute of Ecosystem Studies, an independent environmental research organization based in Millbrook, New York, thinks she has found a way to do this.

Hidden ACE

Starting in early 2020, right after the emergence of covid, Dr Han and colleagues focused their attention on ACE2, a cell membrane protein that had been identified almost immediately as the entry point for the virus. ACE2The day job is to help regulate blood pressure, and most vertebrates have it in one form or another. The researchers wanted to determine in which other species of vertebrates SARSVSoV-2 might expect to bind to the local as strongly ACE2 receptors as to those of human beings. These would be candidates for the role of reservoirs.

To this end, they gathered molecular information on each version of ACE2 that they could get their hands on. Most of them were mammals, 142 of which were species. They then used computer modeling of the interatomic forces involved to determine the strengths of the links likely to develop between SARSVSoVthe peak protein of -2 and each version of ACE2. As they expected, according to news that broke while they were doing their work, the connection to the mink ACE2 was particularly strong. They found an equally strong affinity with ACE2 white-tailed deer, long before any reports of infection in this species appeared. Cats and dogs were also found to be at risk, which reports later confirmed. And gorillas and macaques, which have suffered a few cases in zoos, also seemed susceptible.

As useful as this information was, Dr. Han wanted to go beyond these 142 species. To go further, the team built a database of evolutionary traits shared by the most vulnerable species. ACE2 receivers. This is a technique that has been used successfully in the past on rodents and bats, to assess their likelihood of acting as reservoirs of viruses, including Ebola and Zika. It is based on the idea that particular proteins from species with similar physiologies and lifestyles could evolve in similar ways.

The researchers studied everything they could – from the extent of diet, metabolic rate and age of sexual maturity to litter size, lifespan, geographic distribution, and phylogenetic relationships. – on more than 5,000 mammals for which little or no ACE2-information on the receivers was available. With that huge database completed, they fed the results into a machine learning system that had been trained on the characteristics of the 142 species they had already examined. The result was the revelation of 540 species that seemed likely to have vulnerabilities. ACE2 receptors and therefore the potential to function as covid reservoirs.

Most of the primates were on this list, which, given that people are also primates, was expected. Nor, given the suspicions about SARSVSoV-2’s origins, was the inclusion of 35 types of bats as a surprise. Surprises, however, there were. While the common house mouse does not appear to be a risk, which is good news, two of its rodent companions, the rice field rat and the Malayan field rat, both do. Since these species are often preyed upon by domestic cats, themselves now known to be susceptible to viruses, this provides a route through which people could become infected.

Dozens of other species have also been reported as potential reservoirs. These included red foxes and raccoon dogs – two creatures that, like mink, are sometimes bred for their fur – and white-lipped peccaries (pig-like creatures found in South and Central America) and nilgai ( a large Asian antelope), which are occasionally raised, but also hunted and eaten.

Of the most common farm animals, the species of most concern is the water buffalo. It is estimated that there are more than 200m in the world, acting both as beasts of burden and sources of milk. And other frequently hunted animals, such as duiker (another antelope), warty pig and mule deer were also found to be vulnerable, along with some rarities, including two critically endangered antelopes, the addax and the scimitar-horned oryx (photo below), which was once extinct in the wild and is only now being reintroduced. In these cases, the threat weighs less on humans than on the survival of the species concerned.

Pay the bison bill

The wide range of species involved amazes Dr Han. “I never imagined that we would one day see a virus with such a high potential for interspecies infection,” she says. “It seems that there are at least an order of magnitude more species that are susceptible to SARSVSoV-2 infection than any other zoonotic virus I can think of.

Warned, however, is warned. And here there may be a lesson in keeping Arsenal weapons sharp. One of the reasons why Dr. Han’s study took so long from start to publication is the disparate nature of the sources it had to draw on. Scattered as they were in the natural history collections of the world, their assembly took time. Many museums are now working to make their collections accessible electronically. To some, this may seem like a low priority. Work like this suggests not.

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This article appeared in the Science and Technology section of the print edition under the title “Reservoir Dogs.” And cats. And buffaloes… ”

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