Is it possible for animals to be infected with SARS-CoV-2, and if so, which animals are most likely to become infected?
Global infections with the novel SARS-CoV-2 virus have now surpassed 25 million, demonstrating the ease with which the virus spreads in humans. However, over the last six months, there have also been sporadic reports of animals becoming infected with the coronavirus. This is an important consideration both in terms of the spread of the disease and in terms of animals providing a potential reservoir for the disease after its spread in humans has been contained.
A new study published in the Proceedings of the National Academy of Sciences of the United States of America (1), attempts to predict what animals would likely provide a suitable host for the coronavirus. To do this, the research focused on an angiotensin converting enzyme (ACE), specifically, ACE 2. This enzyme serves as a target for the virus spike protein and provides an entry point for the virus into host cells. Studies of the virus have revealed not just that it binds to ACE2, but also the specific regions of the enzyme that it targets for binding. The enzyme itself is a protein, made up of a sequence of amino acids arranged in a particular order and spatial arrangement.
Could animals catch coronavirus?
ACE 2 is highly conserved across mammalian species, meaning the sequence and structure is largely the same. This suggests that SARS-CoV-2 is theoretically capable of infecting a wide variety of mammalian hosts (suggesting the possibility for animals to catch coronavirus). However, this research digs a little deeper. It examines the exact sequences of ACE2 in 410 different vertebrate species. The species examined were mostly mammals (252) but also included birds (72), fish (65), reptiles (17) and amphibians (4). The researchers focused on a particular 25 amino acid sequence that is thought to be the key region of the enzyme that the virus binds to. Comparing how similar this region is to the human sequence allowed the researchers to predict how well the virus would likely bind.
The various species were then classified in terms of how similar to the human sequence they were. For example, in cases where 23 or more amino acids matched the human sequence, animals were given a classification of “very high”. Using this classification system, the 18 species most at risk of infection with SARS-CoV-2 were all primates. Among the species in the next tier were dolphins and whales, some deer species, and some rodents. Many of the more domesticated species such as cats, cattle, and sheep scored a medium classification.
The researchers also examined variations in the structure of the binding site. Identical amino acid sequences may be arranged slightly differently in 3D space and this can have an impact on the binding of the virus. They first looked at how the structure of the binding site varies across humans and found that significant variation was rare. However, when examining structural variation in animal ACE 2, they found that certain mutations that increase the ability of SARS-CoV-2 to bind are more common and are subject to positive selection.
This study will benefit from the emergence of greater knowledge about the impact of mutations in ACE2 on the binding of SARS-CoV-2. Further research is needed in this area, which in turn would strengthen the predictions made by the algorithm used here. However, overall the study sheds light on an important aspect of the SARS-CoV-2 virus. It gives us a good indicator of which animals are most likely to become infected with coronavirus and also highlights the most likely intermediate species that facilitated the virus spread from bats to humans.
Written by Michael McCarthy
1. Damas J, Hughes GM, Keough KC, Painter CA, Persky NS, Corbo M, et al. Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates. Proceedings of the National Academy of Sciences. 2020:202010146.
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