PT  - JOURNAL ARTICLE
AU  - Yang, Ziwei
AU  - Han, Yang
AU  - Ding, Shilei
AU  - Finzi, Andrés
AU  - Mothes, Walther
AU  - Lu, Maolin
TI  - SARS-CoV-2 variants exhibit increased kinetic stability of open spike conformations as an evolutionary strategy
AID  - 10.1101/2021.10.11.463956
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.11.463956
4099  - http://biorxiv.org/content/early/2021/10/12/2021.10.11.463956.short
4100  - http://biorxiv.org/content/early/2021/10/12/2021.10.11.463956.full
AB  - SARS-CoV-2 variants of concern harbor mutations in the Spike (S) glycoprotein that confer more efficient transmission and dampen the efficacy of COVID-19 vaccines and antibody therapies. S mediates virus entry and is the primary target for antibody responses. Structural studies of soluble S variants have revealed an increased propensity towards conformations accessible to receptor human Angiotensin-Converting Enzyme 2 (hACE2). However, real-time observations of conformational dynamics that govern the structural equilibriums of the S variants have been lacking. Here, we report single-molecule Förster Resonance Energy Transfer (smFRET) studies of S variants containing critical mutations, including D614G and E484K, in the context of virus particles. Investigated variants predominantly occupied more open hACE2-accessible conformations, agreeing with previous structures of soluble trimers. Additionally, these S variants exhibited decelerated transitions in hACE2-accessible/bound states. Our finding of increased S kinetic stability in the open conformation provides a new perspective on SARS-CoV-2 adaptation to the human population.Competing Interest StatementThe authors have declared no competing interest.