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Analysis reveals broad host range of SARS-CoV-2

A new study by the University of California, Davis, has revealed that SARS-CoV-2 may be a threat to other species.


Previous comparative analyses have shown that SARS-CoV and SARS-CoV-2 likely had ancestors that originated in bats. Researchers suggest this was followed by transmission to an intermediate host and then extended to primates and other mammals. In mammalian hosts, coronaviruses often cause severe clinical disease, including respiratory and enteric disease. Understanding the host range of SARS-CoV-2 and other coronaviruses can assist in our ability to predict and control future pandemics.

In this recent study published in PNAS, researchers performed a combination of comparative genomic approaches and protein structural analysis to compare the angiotensin converting enzyme-2 (ACE2) across 410 different species of vertebrate. ACE2 is the main cellular receptor for viral entry in humans. In humans, 25 amino acids of the protein are key for viral binding and entry into the host cells. Therefore, researchers assessed the homology of these 25 amino acids across vertebrate species (including fishes, amphibians, birds, reptiles and mammals) and assessed the ability of each protein structure to bind to SARS-CoV-2 spike (S) protein.

SARS-CoV-2 threatened species

The team designed a five-category binding score based on conservation properties of the 25 amino acids. They found that only mammals fell into the medium to very high categories, which suggests that they are at high risk for SARS-CoV-2 infection. In particular, catarrhine primates scored very high for binding; therefore, researchers predicted these primates at very high risk for SARS-CoV-2 infection. Overall, among species that were most susceptible, 40% were classified as “threatened” by the International Union of Conservation of Nature (IUCN).

Analysis of the ACE2 receptor also revealed that important residues for binding are actively evolving rapidly across mammals. In fact, distinct signatures of positive selection have been found in bat ACE2 and in SARS-CoV-2 protein indicating that bats are evolving to tolerate SARS-CoV-2-like viruses.

This analysis has highlighted a large number of mammals that are at risk of potential SARS-CoV-2 infection via ACE2. This provides insight into the identification of intermediate hosts. Therefore, this can assist in reducing opportunities for future outbreaks. Furthermore, researchers predicted several critically endangered primate species at very high risk of infection. As a result, it is possible that humans could inadvertently introduce this virus into already vulnerable populations. However, the authors urge caution due to the limited infectivity data for the species studied.

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