Researchers at Hunan University Analyze Cellular Receptor ACE2 to Predict Possible Animals That Gave Us Coronavirus

Original scientific paper with images accessible via the following link:

As researchers at the Hunan University in Changsha China suggest, the reservoir species for human coronavirus (COVID-19) is the Chinese horseshoe bat because of high genetic similarity (closely matched gene sequences) between COVID-19 and bat coronavirus (BatCoV RaTG13). The reservoir species has immunity to the virus and can fight it off much like human immunity to the common cold; for this reason, the virus stays within the population without killing many individuals. In other words, horseshoe bats act as the reservoir by maintaining coronaviruses circulating in the environment. When the virus spreads to a new species (e.g. humans) that has no immunity to it, there can be immediate and deadly consequences. This phenomenon is called zoonotic disease and is how most modern epidemics arise (e.g. SARS from civet cats, MERS from camels).

Despite clear evidence that the original reservoir is bats, there is still concern regarding how the virus was transmitted to humans. Lack of direct contact between humans and bats in Wuhan suggest the existence of an intermediate host species that came into contact with both bats and humans. To predict the intermediate host, these inquisitive researchers used the similarities between the Angiotensin-converting enzyme 2 (ACE2) receptor in humans and other mammals in the area of the original epidemic.

You may be wondering how receptors can be used to determine the intermediate host species. Firstly, it is essential to understand that receptors are proteins on the surface of our cells that detect signals or modify other molecules. The receptor ACE2 processes the hormone (a type of molecule that helps cells communicate) angiotensin to regulate blood pressure. Coronaviruses like COVID-19 (SARS-CoV-2) and SARS (SARS-CoV) can highjack this receptor and use it to enter our cells. Once inside, coronaviruses can use the cellular components to replicate themselves, spread between cells inside the body, and eventually transmit to another human.

All vertebrates (animals with a spine) have ACE2 on their cell surfaces with a slightly different structure. COVID-19 is sensitive to these variations and can only affect certain species. By looking at the structural similarities between human ACE2 and that of other animals, these researchers narrowed down the species that likely gave humans COVID-19.

Proteins are produced from a sequence of biological molecules called amino acids. Our DNA sequence dictates the sequence of amino acids in the thousands of different proteins in our body. Using the sequences of amino acids, the researchers produced a phylogenetic tree, which is like a family tree for species (see cited link for image). This tree compares the evolution and relatedness of amino acid sequences of ACE2 protein receptors of various vertebrates in the area of Wuhan. The results of the amino acid analysis indicate that human ACE2s are similar in sequence to the structure of Chinese horseshoe bat (reservoir host), civet cat, swine (pig), and mouse. However, from other studies it is known that COVID-19 cannot bind to mouse ACE2, so it is apparent that this information alone cannot be used to predict the intermediate host. This led researchers to believe that they should focus on the critical site of ACE2, which is the exact location on the receptor that COVID-19 binds and uses to enter the cell. Comparing the structures of this critical site should give more insight on which animals COVID-19 can infect. An image of the computer generated critical site is viewable through the cited link.

By looking at a combination of the whole amino acid sequence and amino acids at the critical site, the researcher narrowed down the possible intermediate hosts to pangolins, cats, cows, buffalo, goat, sheep and pigeon. It is possible that the Chinese horseshoe bat gave COVID-19 to one of these species, whom could have transmitted it amongst each other prior to infecting humans. These findings can be used to support policy to improve the health and safety standards in live animal markets by limiting contact between these species to prevent future coronavirus outbreaks.

Works cited: Y. Qiu et al., Predicting the angiotensin converting enzyme 2 (ACE2) utilizing capability as the receptor of SARS-CoV-2,Microbes and Infection,

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