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In blue, the human ACE2 protein and in gray, the coronavirus spike protein. The image shows how the two proteins interact in a lock and key mechanism, which allows the virus to enter the cell and hijack its protein-making machinery to replicate. Credit: Javier Delgado
Ducks, rats, mice, pigs, and chickens had little or no susceptibility to infection.
Humans, followed by ferrets and to a lesser extent cats, civets and dogs are the animals most susceptible to SARS-CoV-2 infection, according to an analysis of ten different species carried out by researchers from the Center for Genomic Regulation (CRG), based in Barcelona.
The findings, published in PLOS Computational Biology, found that ducks, rats, mice, pigs, and chickens had less or no susceptibility to infection compared to humans.
“Knowing which animals are susceptible to SARS-CoV-2 helps us prevent the accumulation of animal reservoirs from which the coronavirus can re-emerge at a later date,” says Luis Serrano, ICREA research professor, director of the CRG and author main study. “Our findings offer a clue as to why minks, which are closely related to the ferret, are being infected by the disease, which is likely made worse by their crowded living conditions and close contact with human workers.”
The binding affinity for ACE2 receptors with the SARS-CoV-2 spike protein in eight different species compared to humans (the blue baseline). Species above the threshold are vulnerable to allowing coronavirus to enter the cell, while those below have a significantly lower or no risk of infection. Credit: Javier Delgado
“Although we also found a potential susceptibility to infection by cats, they do not coexist with humans under the same conditions as other animals, which may explain why so far there are no known cases of people infected by their pets.” adds Dr. Serrano.
In this article ten species were studied. Five species (humans, cats, ferrets, civets, and dogs) have had documented cases of SARS-CoV-2 infection. There are no reports of infection in the other five species: mice, rats, pigs, chickens, and ducks.
The researchers used computer modeling to test how the coronavirus uses its spike proteins, which protrude from the surface of the virus, to infiltrate the cells of different animals. The main entry point on the surface of a cell is the ACE2 receptor, which binds to the spike protein through a lock and key mechanism. There are many different variants of ACE2 within human populations and in different species.
ACE2 receptor variants in humans followed by ferrets, cats, dogs, and civets have the highest binding affinities for the viral spike protein, while mice, rats, chickens, and ducks have low binding energy.
However, the binding affinity alone is not sufficient to measure the susceptibility of a cell to infection. The researchers also tested the “codon adaptation index” of different species, which is the effectiveness of the coronavirus in controlling the machinery of a cell once it has entered. The more efficient the process, the better the coronavirus will be able to create the proteins it needs to replicate.
Humans, chickens and ducks have the highest codon adaptation index, while the other species are less well adapted.
Taking into account both the binding affinity and the codon adaptation index, the researchers conclude that humans, followed by ferrets, cats, civets, and dogs, are the animals most susceptible to coronavirus infection.
They also found that different human variants of ACE2 showed differences in stability and binding to the spike protein, a sensitivity that may be the basis for why some people suffer from severe COVID-19 symptoms.
“We have identified mutations in protein S that drastically reduce the ability of SARS-CoV-2 to enter the cell, protecting the host from the capture of Covid-19,” says Javier Delgado, CRG researcher and first author of the study. “We are now designing miniproteins from the human ACE2 protein to ‘distract’ the virus’s attention from entry into cells and block an infection. If new mutations of the viral spike protein emerge, we could engineer new variants to block them. “
Understanding the infectivity of SARS-CoV-2 in different species can better inform public health measures, help reduce human contact with other susceptible animals, and prevent the possible prolongation of the COVID-19 pandemic.
According to the WHO, since June 2020, 214 human cases of COVID-19 have been identified in Denmark with variants of SARS-CoV-2 associated with farmed minks, including 12 cases with a unique variant, reported on November 5. Preliminary findings indicate that this particular mink-associated variant has moderately decreased sensitivity to neutralizing antibodies, although this has not been demonstrated.
Reference: “In silico mutagenesis of human ECA2 with protein S and translational efficiency explain the infectivity of SARS-CoV-2 in different species” by Javier Delgado Blanco, Xavier Hernandez-Alias, Damiano Cianferoni and Luis Serrano, 7 of December 2020, PLOS Computational Biology.
DOI: 10.1371 / journal.pcbi.1008450
Funding: Ministry of Science and Innovation, Generalitat of Catalonia, “la Caixa” foundation, CERCA centers, Barcelona Institute of Science and Technology and Severo Ochoa Center of Excellence.
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