Document Type
Article
Publication Date
4-2022
Keywords
SARS-CoV; SARS-CoV-2; coronavirus disease 2019; molecular dynamics; conformational change
Abstract
Within the last 2 decades, severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2) have caused two major outbreaks; yet, for reasons not fully understood, the coronavirus disease 2019 pandemic caused by SARS-CoV-2 has been significantly more widespread than the 2003 SARS epidemic caused by SARS-CoV-1, despite striking similarities between these two viruses. The SARS-CoV-1 and SARSCoV-2 spike proteins, both of which bind to host cell angiotensin-converting enzyme 2, have been implied to be a potential source of their differential transmissibility. However, the mechanistic details of prefusion spike protein binding to angiotensin-converting enzyme 2 remain elusive at the molecular level. Here, we performed an extensive set of equilibrium and nonequilibrium microsecond-level all-atom molecular dynamics simulations of SARS-CoV-1 and SARS-CoV-2 prefusion spike proteins to determine their differential dynamic behavior. 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. These results suggest that not only the receptor-binding domain but also other domains such as the N-terminal domain could play a crucial role in the differential binding behavior of SARS-CoV-1 and SARS-CoV-2 spike proteins.
Citation
Kumar, V. G., Ogden, D. S., Isu, U. H., Polasa, A., Losey, J., & Moradi, M. (2022). Prefusion Spike Protein Conformational Changes are Slower in SARS-CoV-2 than in SARS-CoV-1. Journal of Biological Chemistry, 298 (4), 101814. https://doi.org/10.1016/j.jbc.2022.101814
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
