@article{966ce69ee25440fdb07a3bc0774213d6,
title = "Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants",
abstract = "Neutralizing antibodies (nAbs) elicited against the receptor binding site (RBS) of the spike protein of wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are generally less effective against recent variants of concern. RBS residues Glu484, Lys417, and Asn501 are mutated in variants first described in South Africa (B.1.351) and Brazil (P.1). We analyzed their effects on angiotensin-converting enzyme 2 binding, as well as the effects of two of these mutations (K417N and E484K) on nAbs isolated from COVID-19 patients. Binding and neutralization of the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2), which can both bind the RBS in alternative binding modes, are abrogated by K417N, E484K, or both. These effects can be structurally explained by their extensive interactions with RBS nAbs. However, nAbs to the more conserved, cross-neutralizing CR3022 and S309 sites were largely unaffected. The results have implications for next-generation vaccines and antibody therapies.",
author = "Meng Yuan and Deli Huang and Lee, {Chang-Chun D.} and Wu, {Nicholas C.} and Jackson, {Abigail M.} and Xueyong Zhu and Hejun Liu and Linghang Peng and {van Gils}, {Marit J.} and Sanders, {Rogier W.} and Burton, {Dennis R.} and Reincke, {S. Momsen} and Harald Pr{\"u}ss and Jakob Kreye and David Nemazee and Ward, {Andrew B.} and Wilson, {Ian A.}",
note = "Funding Information: Supported by Bill and Melinda Gates Foundation grants OPP1170236 and INV-004923 INV (I.A.W., A.B.W., and D.R.B.); NIH grants R00 AI139445 (N.C.W.), NIH P01 AI110657 (I.A.W., A.B.W., and R.W.S.), R01 AI132317 (D.N. and D.H.), and R01 AI142945 (L.P.); German Research Foundation grants PR 1274/3-1 and PR 1274/5-1, Helmholtz Association grants HIL-A03 and SO-097, and German Federal Ministry of Education and Research Connect-Generate grant 01GM1908D (H.P.); and a Vici fellowship from the Netherlands Organisation for Scientific Research (NWO) (R.W.S.). This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility, operated for the DOE Office of Science by Argonne National Laboratory under contract DE-AC02-06CH11357. Extraordinary facility operations were supported in part by the DOE Office of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national laboratories focused on the response to COVID-19, with funding provided by the Coronavirus CARES Act. Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works",
year = "2021",
month = aug,
day = "13",
doi = "https://doi.org/10.1126/science.abh1139",
language = "English",
volume = "373",
pages = "818--823",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6556",
}