@article{005fd21fa71d4a29a0a62579ca4603a0,
title = "A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection",
abstract = "Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses.",
keywords = "cross-neutralizing antibody, COVID-19, SARS-CoV-2, coronavirus, antibody-antigen interaction, 3D structure, crystallography, synergy, antibody cocktail",
author = "Hejun Liu and Meng Yuan and Deli Huang and Sandhya Bangaru and Fangzhu Zhao and Lee, {Chang Chun D.} and Linghang Peng and Shawn Barman and Xueyong Zhu and David Nemazee and Burton, {Dennis R.} and {van Gils}, {Marit J.} and Sanders, {Rogier W.} and Kornau, {Hans Christian} and Reincke, {S. Momsen} and Harald Pr{\"u}ss and Jakob Kreye and Wu, {Nicholas C.} and Ward, {Andrew B.} and Wilson, {Ian A.}",
note = "Funding Information: We thank Henry Tien for technical support with the crystallization robot, Jeanne Matteson and Yuanzi Hua for contribution to mammalian cell culture, Wenli Yu for insect cell culture, and Robyn Stanfield for assistance in data collection. We acknowledge BIAFFIN GmbH & Co KG (Kassel, Germany) for the help on the SPR competition assay. We are grateful to the staff of the Advanced Photon Source (APS) Beamline 23ID for assistance. This work was supported by the Bill and Melinda Gates Foundation OPP1170236 and INV-004923 (A.B.W., D.R.B., and I.A.W.), NIH R00 AI139445 (N.C.W.) and R01 AI132317 (D.N.), and the German Research Foundation (H.P.). R.W.S. is a recipient of a Vici fellowship from the Netherlands Organization for Scientific Research (NWO). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility, operated for the DOE Office of Science by Argonne National Laboratory under contract no. 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: {\textcopyright} 2021 The Authors",
year = "2021",
month = may,
day = "12",
doi = "10.1101/2021.02.11.430866",
language = "English (US)",
volume = "29",
pages = "806--818.e6",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "5",
}