Prefusion spike protein conformational changes are slower in SARS-CoV-2 than in SARS-CoV-1
by Kumar, Vivek Govind; Ogden, Dylan S.; Isu, Ugochi H.; Polasa, Adithya; Losey, James; Moradi, Mahmoud
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.
- Journal
- Journal of Biological Chemistry
- Volume
- 298
- Issue
- 4
- Year
- 2022
- URL
- https://dx.doi.org/10.1016/j.jbc.2022.101814
- ISBN/ISSN
- 1083-351X; 0021-9258
- DOI
- 10.1016/j.jbc.2022.101814