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Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics.
Braet, Sean M; Buckley, Theresa S C; Venkatakrishnan, Varun; Dam, Kim-Marie A; Bjorkman, Pamela J; Anand, Ganesh S.
  • Braet SM; Department of Chemistry, Pennsylvania State University, University Park, United States.
  • Buckley TSC; Department of Chemistry, Pennsylvania State University, University Park, United States.
  • Venkatakrishnan V; Department of Chemistry, Pennsylvania State University, University Park, United States.
  • Dam KA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
  • Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
  • Anand GS; Department of Chemistry, Pennsylvania State University, University Park, United States.
Elife ; 122023 03 17.
Article in English | MEDLINE | ID: covidwho-2252894
ABSTRACT
SARS-CoV-2 emergent variants are characterized by increased viral fitness and each shows multiple mutations predominantly localized to the spike (S) protein. Here, amide hydrogen/deuterium exchange mass spectrometry has been applied to track changes in S dynamics from multiple SARS-CoV-2 variants. Our results highlight large differences across variants at two loci with impacts on S dynamics and stability. A significant enhancement in stabilization first occurred with the emergence of D614G S followed by smaller, progressive stabilization in subsequent variants. Stabilization preceded altered dynamics in the N-terminal domain, wherein Omicron BA.1 S showed the largest magnitude increases relative to other preceding variants. Changes in stabilization and dynamics resulting from S mutations detail the evolutionary trajectory of S in emerging variants. These carry major implications for SARS-CoV-2 viral fitness and offer new insights into variant-specific therapeutic development.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Topics: Variants Limits: Humans Language: English Year: 2023 Document Type: Article Affiliation country: ELife.82584

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Topics: Variants Limits: Humans Language: English Year: 2023 Document Type: Article Affiliation country: ELife.82584