Mary Wilson
Well-known member
Science Advances 16 Apr 2021:
Vol. 7, no. 16, eabf3671
DOI: 10.1126/sciadv.abf3671
Rachael A. Mansbach[SUP]1[/SUP],?,?, Srirupa Chakraborty[SUP]1[/SUP],[SUP]2[/SUP],?, Kien Nguyen[SUP]1[/SUP],?, David C. Montefiori[SUP]3[/SUP], Bette Korber[SUP]1[/SUP] and S. Gnanakaran[SUP]1[/SUP]
Abstract
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 ?Spike? protein. 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.
https://advances.sciencemag.org/content/7/16/eabf3671
Vol. 7, no. 16, eabf3671
DOI: 10.1126/sciadv.abf3671
Rachael A. Mansbach[SUP]1[/SUP],?,?, Srirupa Chakraborty[SUP]1[/SUP],[SUP]2[/SUP],?, Kien Nguyen[SUP]1[/SUP],?, David C. Montefiori[SUP]3[/SUP], Bette Korber[SUP]1[/SUP] and S. Gnanakaran[SUP]1[/SUP]
Abstract
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 ?Spike? protein. 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.
https://advances.sciencemag.org/content/7/16/eabf3671