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bioRxiv · 10.1101/2021.10.11.463956

SARS-CoV-2 variants exhibit increased kinetic stability of open spike conformations as an evolutionary strategy

Yang, Z.·Han, Y.·Ding, S.·Finzi, A.·Mothes, W.·Lu, M.
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Abstract

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 Forster 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.

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Yang, Z., Han, Y., Ding, S., Finzi, A., Mothes, W., Lu, M.. 2021-10-12. SARS-CoV-2 variants exhibit increased kinetic stability of open spike conformations as an evolutionary strategy. https://doi.org/10.1101/2021.10.11.463956

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