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Article: Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike

TitlePotent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike
Authors
Keywordsamino terminal sequence
animal experiment
animal model
animal tissue
clinical article
Issue Date2020
PublisherNature Research (part of Springer Nature). The Journal's web site is located at http://www.nature.com/nature
Citation
Nature, 2020, v. 584 n. 7821, p. 450-456 How to Cite?
AbstractThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this coronavirus. Here we report the isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Among these are nineteen antibodies that potently neutralized authentic SARS-CoV-2 in vitro, nine of which exhibited very high potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng ml-1. Epitope mapping showed that this collection of nineteen antibodies was about equally divided between those directed against the receptor-binding domain (RBD) and those directed against the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody that targets the RBD, a second that targets the NTD, and a third that bridges two separate RBDs showed that the antibodies recognize the closed, 'all RBD-down' conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.
Persistent Identifierhttp://hdl.handle.net/10722/289441
ISSN
2019 Impact Factor: 42.778
2015 SCImago Journal Rankings: 21.936

 

DC FieldValueLanguage
dc.contributor.authorLiu, L-
dc.contributor.authorWang, P-
dc.contributor.authorNair, MS-
dc.contributor.authorYu, J-
dc.contributor.authorRapp, M-
dc.contributor.authorWang, Q-
dc.contributor.authorLuo, Y-
dc.contributor.authorChan, JFW-
dc.contributor.authorSahi, V-
dc.contributor.authorFigueroa, A-
dc.contributor.authorGuo, XV-
dc.contributor.authorCerutti, G-
dc.contributor.authorBimela, J-
dc.contributor.authorGorman, J-
dc.contributor.authorZhou, T-
dc.contributor.authorChen, Z-
dc.contributor.authorYuen, KY-
dc.contributor.authorKwong, PD-
dc.contributor.authorSodroski, JG-
dc.contributor.authorYin, MT-
dc.contributor.authorSheng, Z-
dc.contributor.authorHuang, Y-
dc.contributor.authorShapiro, L-
dc.contributor.authorHo, DD-
dc.date.accessioned2020-10-22T08:12:42Z-
dc.date.available2020-10-22T08:12:42Z-
dc.date.issued2020-
dc.identifier.citationNature, 2020, v. 584 n. 7821, p. 450-456-
dc.identifier.issn0028-0836-
dc.identifier.urihttp://hdl.handle.net/10722/289441-
dc.description.abstractThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this coronavirus. Here we report the isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Among these are nineteen antibodies that potently neutralized authentic SARS-CoV-2 in vitro, nine of which exhibited very high potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng ml-1. Epitope mapping showed that this collection of nineteen antibodies was about equally divided between those directed against the receptor-binding domain (RBD) and those directed against the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody that targets the RBD, a second that targets the NTD, and a third that bridges two separate RBDs showed that the antibodies recognize the closed, 'all RBD-down' conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.-
dc.languageeng-
dc.publisherNature Research (part of Springer Nature). The Journal's web site is located at http://www.nature.com/nature-
dc.relation.ispartofNature-
dc.rightsThis is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: https://doi.org/[insert DOI]-
dc.subjectamino terminal sequence-
dc.subjectanimal experiment-
dc.subjectanimal model-
dc.subjectanimal tissue-
dc.subjectclinical article-
dc.titlePotent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike-
dc.typeArticle-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityChen, Z=rp00243-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/s41586-020-2571-7-
dc.identifier.pmid32698192-
dc.identifier.scopuseid_2-s2.0-85088399616-
dc.identifier.hkuros317145-
dc.identifier.volume584-
dc.identifier.issue7821-
dc.identifier.spage450-
dc.identifier.epage456-
dc.publisher.placeUnited Kingdom-

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