Differential Dynamic Behavior of Prefusion Spike Proteins of SARS Coronaviruses 1 and 2

The coronavirus spike protein, which binds to the same human receptor in both SARS-CoV-1 and 2, has been implied to be a potential source of their differential transmissibility. However, the mechanistic details of spike protein binding to its human receptor remain elusive at the molecular level. Her...

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Bibliographic Details
Published in:bioRxiv 2021-03
Main Authors: Vivek Govind Kumar, Ogden, Dylan S, Isu, Ugochi H, Polasa, Adithya, Losey, James, Moradi, Mahmoud
Format: Article
Language:English
Subjects:
Coronaviruses
Protein structure
Proteins
Severe acute respiratory syndrome coronavirus 2
Spike protein
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Summary:The coronavirus spike protein, which binds to the same human receptor in both SARS-CoV-1 and 2, has been implied to be a potential source of their differential transmissibility. However, the mechanistic details of spike protein binding to its human receptor remain elusive at the molecular level. Here, we have used an extensive set of unbiased and biased microsecond-level all-atom molecular dynamics (MD) simulations of SARS-CoV-1 and 2 spike proteins to determine the differential dynamic behavior of prefusion spike protein structure in the two viruses. Our results indicate that the active form of the SARS-CoV-2 spike protein is more stable than that of SARS-CoV-1 and the energy barrier associated with the activation is higher in SARS-CoV-2. Our results also suggest that not only the receptor binding domain (RBD) but also other domains such as the N-terminal domain (NTD) could play a role in the differential binding behavior of SARS-CoV-1 and 2 spike proteins. Competing Interest Statement The authors have declared no competing interest. Footnotes * The abstract is shortened. Several references are added. Minor changes made to the manuscript.
DOI:10.1101/2020.12.25.424008