High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme

Abstract There are currently few approved effective treatments for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Nanobodies are 12–15 kDa single-domain antibody fragments that can be delivered by inhalation and are amenable to relatively inexpensive large scale production compared to...

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Autores principales:	Thomas J. Esparza, Negin P. Martin, George P. Anderson, Ellen R. Goldman, David L. Brody
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/781613999e5f4819ab8747154b1624dd
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spelling	oai:doaj.org-article:781613999e5f4819ab8747154b1624dd2021-12-02T11:59:40ZHigh affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme10.1038/s41598-020-79036-02045-2322https://doaj.org/article/781613999e5f4819ab8747154b1624dd2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79036-0https://doaj.org/toc/2045-2322Abstract There are currently few approved effective treatments for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Nanobodies are 12–15 kDa single-domain antibody fragments that can be delivered by inhalation and are amenable to relatively inexpensive large scale production compared to other biologicals. We have isolated nanobodies that bind to the SARS-CoV-2 spike protein receptor binding domain and block spike protein interaction with the angiotensin converting enzyme 2 (ACE2) with 1–5 nM affinity. The lead nanobody candidate, NIH-CoVnb-112, blocks SARS-CoV-2 spike pseudotyped lentivirus infection of HEK293 cells expressing human ACE2 with an EC50 of 0.3 µg/mL. NIH-CoVnb-112 retains structural integrity and potency after nebulization. Furthermore, NIH-CoVnb-112 blocks interaction between ACE2 and several high affinity variant forms of the spike protein. These nanobodies and their derivatives have therapeutic, preventative, and diagnostic potential.Thomas J. EsparzaNegin P. MartinGeorge P. AndersonEllen R. GoldmanDavid L. BrodyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thomas J. Esparza Negin P. Martin George P. Anderson Ellen R. Goldman David L. Brody High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme
description	Abstract There are currently few approved effective treatments for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Nanobodies are 12–15 kDa single-domain antibody fragments that can be delivered by inhalation and are amenable to relatively inexpensive large scale production compared to other biologicals. We have isolated nanobodies that bind to the SARS-CoV-2 spike protein receptor binding domain and block spike protein interaction with the angiotensin converting enzyme 2 (ACE2) with 1–5 nM affinity. The lead nanobody candidate, NIH-CoVnb-112, blocks SARS-CoV-2 spike pseudotyped lentivirus infection of HEK293 cells expressing human ACE2 with an EC50 of 0.3 µg/mL. NIH-CoVnb-112 retains structural integrity and potency after nebulization. Furthermore, NIH-CoVnb-112 blocks interaction between ACE2 and several high affinity variant forms of the spike protein. These nanobodies and their derivatives have therapeutic, preventative, and diagnostic potential.
format	article
author	Thomas J. Esparza Negin P. Martin George P. Anderson Ellen R. Goldman David L. Brody
author_facet	Thomas J. Esparza Negin P. Martin George P. Anderson Ellen R. Goldman David L. Brody
author_sort	Thomas J. Esparza
title	High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme
title_short	High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme
title_full	High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme
title_fullStr	High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme
title_full_unstemmed	High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme
title_sort	high affinity nanobodies block sars-cov-2 spike receptor binding domain interaction with human angiotensin converting enzyme
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/781613999e5f4819ab8747154b1624dd
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High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme

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