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Prefusion spike protein conformational changes are slower in SARS-CoV-2 than in SARS-CoV-1.
Govind Kumar, Vivek; Ogden, Dylan S; Isu, Ugochi H; Polasa, Adithya; Losey, James; Moradi, Mahmoud.
  • Govind Kumar V; Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, USA.
  • Ogden DS; Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, USA.
  • Isu UH; Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, USA.
  • Polasa A; Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, USA.
  • Losey J; Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, USA.
  • Moradi M; Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, USA. Electronic address: moradi@uark.edu.
J Biol Chem ; 298(4): 101814, 2022 04.
Article in English | MEDLINE | ID: covidwho-1788109
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 SARS-CoV-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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / SARS-CoV-2 Limits: Humans Language: English Journal: J Biol Chem Year: 2022 Document Type: Article Affiliation country: J.jbc.2022.101814

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / SARS-CoV-2 Limits: Humans Language: English Journal: J Biol Chem Year: 2022 Document Type: Article Affiliation country: J.jbc.2022.101814