Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs...

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Autores principales:	Kei Haga, Reiko Takai-Todaka, Yuta Matsumura, Chihong Song, Tomomi Takano, Takuto Tojo, Atsushi Nagami, Yuki Ishida, Hidekazu Masaki, Masayuki Tsuchiya, Toshiki Ebisudani, Shinya Sugimoto, Toshiro Sato, Hiroyuki Yasuda, Koichi Fukunaga, Akihito Sawada, Naoto Nemoto, Kazuyoshi Murata, Takuya Morimoto, Kazuhiko Katayama
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/977c1f70bb2049c3a2f6faef7c65e0e7
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spelling	oai:doaj.org-article:977c1f70bb2049c3a2f6faef7c65e0e72021-11-25T05:45:51ZNasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model.1553-73661553-737410.1371/journal.ppat.1009542https://doaj.org/article/977c1f70bb2049c3a2f6faef7c65e0e72021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009542https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed, particularly for treating life-threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited SARS-CoV-2 titers in infected lungs of Syrian hamsters without causing weight loss and cytokine induction. In vitro studies demonstrated that K-874A neutralized SARS-CoV-2 in both VeroE6/TMPRSS2 and human lung-derived alveolar organoid cells. Unlike other drug candidates, K-874A blocks viral membrane fusion rather than viral attachment. Cryo-electron microscopy revealed K-874A bound between the receptor binding domain and N-terminal domain of the virus S protein. Further, infected cells treated with K-874A produced fewer virus progeny that were less infective. We propose that direct administration of K-874A to the lung could be a new treatment for preventing the reinfection of amplified virus in COVID-19 patients.Kei HagaReiko Takai-TodakaYuta MatsumuraChihong SongTomomi TakanoTakuto TojoAtsushi NagamiYuki IshidaHidekazu MasakiMasayuki TsuchiyaToshiki EbisudaniShinya SugimotoToshiro SatoHiroyuki YasudaKoichi FukunagaAkihito SawadaNaoto NemotoKazuyoshi MurataTakuya MorimotoKazuhiko KatayamaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 10, p e1009542 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Kei Haga Reiko Takai-Todaka Yuta Matsumura Chihong Song Tomomi Takano Takuto Tojo Atsushi Nagami Yuki Ishida Hidekazu Masaki Masayuki Tsuchiya Toshiki Ebisudani Shinya Sugimoto Toshiro Sato Hiroyuki Yasuda Koichi Fukunaga Akihito Sawada Naoto Nemoto Kazuyoshi Murata Takuya Morimoto Kazuhiko Katayama Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model.
description	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed, particularly for treating life-threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited SARS-CoV-2 titers in infected lungs of Syrian hamsters without causing weight loss and cytokine induction. In vitro studies demonstrated that K-874A neutralized SARS-CoV-2 in both VeroE6/TMPRSS2 and human lung-derived alveolar organoid cells. Unlike other drug candidates, K-874A blocks viral membrane fusion rather than viral attachment. Cryo-electron microscopy revealed K-874A bound between the receptor binding domain and N-terminal domain of the virus S protein. Further, infected cells treated with K-874A produced fewer virus progeny that were less infective. We propose that direct administration of K-874A to the lung could be a new treatment for preventing the reinfection of amplified virus in COVID-19 patients.
format	article
author	Kei Haga Reiko Takai-Todaka Yuta Matsumura Chihong Song Tomomi Takano Takuto Tojo Atsushi Nagami Yuki Ishida Hidekazu Masaki Masayuki Tsuchiya Toshiki Ebisudani Shinya Sugimoto Toshiro Sato Hiroyuki Yasuda Koichi Fukunaga Akihito Sawada Naoto Nemoto Kazuyoshi Murata Takuya Morimoto Kazuhiko Katayama
author_facet	Kei Haga Reiko Takai-Todaka Yuta Matsumura Chihong Song Tomomi Takano Takuto Tojo Atsushi Nagami Yuki Ishida Hidekazu Masaki Masayuki Tsuchiya Toshiki Ebisudani Shinya Sugimoto Toshiro Sato Hiroyuki Yasuda Koichi Fukunaga Akihito Sawada Naoto Nemoto Kazuyoshi Murata Takuya Morimoto Kazuhiko Katayama
author_sort	Kei Haga
title	Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model.
title_short	Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model.
title_full	Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model.
title_fullStr	Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model.
title_full_unstemmed	Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model.
title_sort	nasal delivery of single-domain antibody improves symptoms of sars-cov-2 infection in an animal model.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/977c1f70bb2049c3a2f6faef7c65e0e7
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Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model.

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