Insights on the mutational landscape of the SARS-CoV-2 Omicron variant receptor-binding domain
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1-s2.0-S2666379122000271-main.pdf
Description
Published version
Size
1.81 MB
Format
Adobe PDF
Checksum (MD5)
e173f6224adbd50e183383bf4084f8f9
Author(s)
Miller, Nathaniel L
Clark, Thomas
Raman, Rahul
Sasisekharan, Ram
Date Issued
2022
Journal
Cell Reports Medicine
Publisher
Elsevier BV
Citation
Miller, Nathaniel L, Clark, Thomas, Raman, Rahul and Sasisekharan, Ram. 2022. "Insights on the mutational landscape of the SARS-CoV-2 Omicron variant receptor-binding domain." Cell Reports Medicine, 3 (2).
Version
Final published version
Abstract
The Omicron variant features enhanced transmissibility and antibody escape. Here, we describe the Omicron receptor-binding domain (RBD) mutational landscape using amino acid interaction (AAI) networks, which are well suited for interrogating constellations of mutations that function in an epistatic manner. Using AAI, we map Omicron mutations directly and indirectly driving increased escape breadth and depth in class 1-4 antibody epitopes. Further, we present epitope networks for authorized therapeutic antibodies and assess perturbations to each antibody's epitope. Since our initial modeling following the identification of Omicron, these predictions have been realized by experimental findings of Omicron neutralization escape from therapeutic antibodies ADG20, AZD8895, and AZD1061. Importantly, the AAI predicted escape resulting from indirect epitope perturbations was not captured by previous sequence or point mutation analyses. Finally, for several Omicron RBD mutations, we find evidence for a plausible role in enhanced transmissibility via disruption of RBD-down conformational stability at the RBDdown-RBDdown interface.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.XCRM.2022.100527
