Journal
SCIENCE ADVANCES
Volume 7, Issue 16, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abf3671
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Funding
- Los Alamos National Laboratory (LANL) Director's Postdoctoral Fellowship
- Center of Nonlinear Studies Postdoctoral Program
- Spatiotemporal Modeling Center at the University of New Mexico [NIH P50GM085273]
- LANL LDRD project [20200706ER]
- U.S. Department of Energy National Nuclear Security Administration [89233218CNA000001]
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The emergence of the G-form variant of COVID-19 has led to a more infectious strain with increased viral loads, likely due to changes in protein energetics favoring infection-capable states and enhanced exposure of the receptor binding domain. These findings are crucial for vaccine design.
The COVID-19 (coronavirus disease 2019) 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 Spikeprotein. The G-form is more infectious in vitro and is associated with increased viral loads in the upper airways. To gain insight into the molecular-level underpinnings of these characteristics, we used microsecond all-atom simulations. We show that changes in the protein energetics favor a higher population of infection-capable states in the G-form through release of asymmetry present in the D-form inter-protomer interactions. 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 owing to enhanced exposure of the receptor binding domain, a key target region for neutralizing antibodies. These results are critical for vaccine design.
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