How do we know what species can be infected by SARS-

CoV-2?
By Tara Wirsching

6/7/2020

Hello everyone, This time around I will be reviewing the paper “Spike protein recognition of
mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection” by
Junwen Luan, Yue Lu, Xiaolu Jin, and Leiliang Zhang. This paper explores which animals might be
susceptible to infections of SARS-CoV-2 through computer simulations.

In my last blog post I covered the paper “The Proximal Origin of SARS-CoV-2” by Andersen et
al. This paper provided evidence that the virus is the product of evolution and not a engeneered in a lab
due to the novel mutations and the innefficiencies predicted in the bonding of the Spike proteins of the
virus with human ACE cell receptors.

The SARS-CoV-2 genome

The SARS-CoV-2 virus’ genome is comprised of a single stranded RNA molecule that is 30 kb
long[ CITATION Lua20 \l 1033 ]. The genome codes for 4 major structural proteins that are the Spike
protein, the membrane protein, the envelope protein and the nucleocapside prtein. The spike protein is of
interests to scientists due to its role in binding to host cell receptors and tricking the host cell to let it in
and infect the host cell.

The Spike protein interactions!

As stated in the “The Proximal Origin of SARS-CoV-2” by Andersen et al. the S-proteins is most similar
to the SARS-like virus from Pangolins. Through computer simulations using DNA sequences to build
models of both the ACE receptor proteins and the SARS-CoV-2’s spike protien. The simulation focused
on the amino acids fo the spike protien L455, F486,Q493, S494, N501 and Y505 and the amino acids
Y442, L472, N479, D480, T487, Y491 from human ACE2 receptors (hACE2). The intraction between
these two groups of amino acids was used to predict if other ACE and ACE-like receptors in other
mammalian species reacted the same way as hACE2 to the SARS-CoV-2 spike protein.
 Figure 1. Aligment of RBM region of S proteins from SARS-CoV and Sars-CoV illustrates an
example of Taking genome sequences (shown under pat A) and building a computer model
(shown in Blue/green squigly lines under part B). The human ACE2 receptor (hACE2) with its
known structure is shown in red. The zoomed in box shows the key amino acids where the two
proteins intereact. This interaction is key for the virus being able to enter and infect cells.

From the simulation it was predicted that ACE receptors from Camelus dromedarius, Procyon
lotor, Rhinolophus ferrumequinum, Rattus norvegicus, Mus musculus, Ornithorhynchus
anatinus, Loxodonta africana, Erinaceus europaeus, Nyctereutes procyonoides, Suricata
suricatta, Dipodomys ordii, and Cavia porcellus could not bind to SARS-CoV-2’s spike
protiens[ CITATION Lua20 \l 1033 ]. However, the S-protein could bind to ACE receptors from Homo
sapiens, Rhinopithecus roxellana, Macaca mulatta, Mustela erminea, Paguma larvata, Rhinolophus
macrotis, Rhinolophus sinicus, Rousettus leschenaultii, Sus scrofa, Mustela putorius furo, Canis lupus
familiaris, Felis catus, Manis javanica (pangolin), Rhinolophus pearsonii, Pteropus vampyrus, Pongo
abelii, Equus caballus, Bos taurus, Pan troglodytes, Ovis aries, Papio Anubis, Sus scrofa
domesticus, Oryctolagus cuniculus, Vulpes vulpes, Phodopus campbelli, Mesocricetus auratus, Callithrix
jacchus, Heterocephalus glaber, Ictidomys tridecemlineatus, and Cricetulus griseus (Chinese hamster)
[ CITATION Lua20 \l 1033 ]. This list includes domestic pets like cats and dogs. As a result, domestic
animals should be monitored moving forward to verify if they can become infected by SARS-CoV-2.

Some of the small animals such as the chinese hamster nad golden hamster are succeptible to SARS-
CoV-2 and could be used in the development for medications against COVID-19 or a Vaccine that would
protect against SARS-CoV-2 viral infections. Unfortunately, the mouse, commonly used in testing for
human medications, cannot be used since it is outside the host range of SARS-CoV-2 and therefore
cannot be infected. However, there are transgenic mice that have been genetically modified to have
hACE2 instead of mouse ACE receptors. These mice could be useful to further study how the virus
interacts with hACE2 and control for any unknown differences between how SARS-CoV-2 interacts with
hamster ACE receptors.

Works Cited
Andersen, K. G., Rambaut, A., Lipkin, W. I., Holmes, E. C., & Garry, R. F. (2020, March 17). The
Proximal Origin of SARS-COV-2. Nature Medicine(26), pp. 450-452.
doi:https://doi.org/10.1038/s41591-020-0820-9

Luan, J., Lu, Y., Jin, X., & Zhang, L. (2020). Spike protein recognition of mammalian ACE2 predicts the
host range and an optimized ACE2 for SARS-CoV-2 infection. ELSEVIER, 526(1), 165-169.
doi:https://doi.org/10.1016/j.bbrc.2020.03.047

World Health Organization. (2020, May 26). Conavirus disease 2019. Retrieved from World Health
Organization: https://www.who.int/emergencies/diseases/novel-coronavirus-2019

World Health Organization. (2020, March 27). WHO Coronavirus Disease (COVID-19) Dashboard.
Retrieved from World Health Organization: https://covid19.who.int/