The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State
- Concordia University, Montreal, Quebec, Canada; Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Los Alamos National Laboratory
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Duke Human Vaccine Institute & Department of Surgery
The COVID-19 pandemic underwent a rapid transition with the emergence of a dominant viral variant (from the “D-form” to the “G-form”) that carried an amino acid substitution D614G in its “Spike” protein. The G-form is more infectious in vitro and associated with increased viral loads. To gain insight into the molecular-level underpinnings of these characteristics, we employed microsecond all-atom simulations. Here we show that changes in the protein energetics favor a higher population of infection-capable (open) states through release of hydrogen bonds of an asymmetry present in the D-form but not the G-form. Thus, the increased infectivity of the G-form is likely due to a higher rate of profitable binding encounters with the host receptor. It is also predicted to be more neutralization sensitive due to enhanced exposure of the receptor binding domain, a key target region for neutralizing antibodies. These results are significant for vaccine design. The Molecular Dynamics Simulations datasets generated in this study, namely that of the soluble form SARS-CoV-2 Spike protein are made available here. Details of the trajectory and supporting files are given in the README.txt file.
- Research Organization:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Organization:
- USDOE Laboratory Directed Research and Development (LDRD) Program
- DOE Contract Number:
- 89233218CNA000001
- OSTI ID:
- 1760388
- Report Number(s):
- LA-UR-21-20410
- Country of Publication:
- United States
- Language:
- English
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