An analysis and structural modeling of the SARS-CoV-2 spike protein, the area of the virus that facilitates entry into a cell, reveals a unique feature that could explain why the COVID-19-causing coronavirus is so transmissible between people. The study also shows that, aside from primates, cats, ferrets and minks are the animal species apparently most susceptible to the SARS-CoV-2 virus.
Colorized scanning electron micrograph of an apoptotic cell (red) infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Image credit: NIAID.
In the study, Professor Gary Whittaker from the Department of Microbiology & Immunology at Cornell University and colleagues identified a structural loop in the SARS-CoV-2 spike protein and a sequence of four amino acids in this loop that is different from other known human coronaviruses in this viral lineage.
The analysis of the lineage of SARS-CoV-2 showed it shared properties of the closely related SARS-CoV-1, which first appeared in humans in 2003 and is lethal but not highly contagious, and HCoV-HKU1, a highly transmissible but relatively benign human coronavirus.
“It got this strange combination of both properties,” Professor Whittaker said.
“The prediction is that the loop is very important to transmissibility or stability, or both.”
“We are focused on further study of this structural loop and the sequence of four amino acids.”
SARS-CoV-2 S1/S2 and S2’ activation sites. The S1/S2 and S2’ activation sites of SARS-CoV-1 and SARSCoV-2 S models are shown in surface and ribbon views. S1/S2 and S2’ sites of bat-CoVs are shown in ribbon view. Amino acid homology to SARS-CoV-1 is noted as follows: S1/S2 site — homology (red) and differences (blue); S2’ site — homology (yellow) and differences (magenta). Amino acid alignments of the S1/S2 and S2’ sites are shown, and homology is also noted. Image credit: Jaimes et al, doi: 10.1016/j.jmb.2020.04.009.
Cats, ferrets and minks are also susceptible, according to the team.
In order to infect a cell, features of the spike protein must bind with a receptor on the host cell’s surface, and cats have a receptor binding site that closely matches that of humans.
To date, infections in cats appear to be mild and infrequent, and there is not evidence that cats can, in turn, infect humans.
“Investigations into feline coronaviruses could provide further clues into SARS-CoV-2 and coronaviruses in general,” Professor Whittaker said.
“We are keeping an open mind to see if similar things may happen in cats that already that are now happening in humans.”
A paper on the findings appears in the Journal of Molecular Biology.
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Javier A. Jaimes et al. Phylogenetic Analysis and Structural Modeling of SARS-CoV-2 Spike Protein Reveals an Evolutionary Distinct and Proteolytically Sensitive Activation Loop. Journal of Molecular Biology, published online April 19, 2020; doi: 10.1016/j.jmb.2020.04.009
This article is based on text provided by Cornell University.
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