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dc.contributor.authorMiller, Nathaniel L
dc.contributor.authorClark, Thomas
dc.contributor.authorRaman, Rahul
dc.contributor.authorSasisekharan, Ram
dc.date.accessioned2023-02-07T14:08:01Z
dc.date.available2023-02-07T14:08:01Z
dc.date.issued2022
dc.identifier.urihttps://hdl.handle.net/1721.1/147927
dc.description.abstractThe 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.en_US
dc.language.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionof10.1016/J.XCRM.2022.100527en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourceCell Reportsen_US
dc.titleInsights on the mutational landscape of the SARS-CoV-2 Omicron variant receptor-binding domainen_US
dc.typeArticleen_US
dc.identifier.citationMiller, 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).
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.relation.journalCell Reports Medicineen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2023-02-07T13:58:29Z
dspace.orderedauthorsMiller, NL; Clark, T; Raman, R; Sasisekharan, Ren_US
dspace.date.submission2023-02-07T13:58:31Z
mit.journal.volume3en_US
mit.journal.issue2en_US
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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