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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| Veröffentlicht in: | PLoS pathogens 2021-10, Vol.17 (10), p.e1009542-e1009542 |
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| creator | Haga, Kei Takai-Todaka, Reiko Matsumura, Yuta Song, Chihong Takano, Tomomi Tojo, Takuto Nagami, Atsushi Ishida, Yuki Masaki, Hidekazu Tsuchiya, Masayuki Ebisudani, Toshiki Sugimoto, Shinya Sato, Toshiro Yasuda, Hiroyuki Fukunaga, Koichi Sawada, Akihito Nemoto, Naoto Murata, Kazuyoshi Morimoto, Takuya Katayama, Kazuhiko |
| 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. |
| doi_str_mv | 10.1371/journal.ppat.1009542 |
| format | Article |
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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.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1009542</identifier><identifier>PMID: 34648602</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Alveoli ; Animal models ; Antibodies ; Antigens ; Antiviral agents ; Biology and life sciences ; Candidates ; Coronaviruses ; COVID-19 ; Cytokines ; Dosage and administration ; Drug development ; Drug dosages ; Electron microscopy ; Enzymes ; Experiments ; Hamsters ; Infections ; Interferometry ; Intranasal medication ; Lungs ; Medicine and health sciences ; Membrane fusion ; Monoclonal antibodies ; Nanobodies ; Organoids ; Progeny ; Proteins ; Research and Analysis Methods ; Respiratory syncytial virus ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Signs and symptoms ; Testing ; Vaccines ; Viral antibodies ; Viral diseases ; Virus attachment ; Viruses ; Weight loss</subject><ispartof>PLoS pathogens, 2021-10, Vol.17 (10), p.e1009542-e1009542</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Haga et al. 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delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model</title><author>Haga, Kei ; Takai-Todaka, Reiko ; Matsumura, Yuta ; Song, Chihong ; Takano, Tomomi ; Tojo, Takuto ; Nagami, Atsushi ; Ishida, Yuki ; Masaki, Hidekazu ; Tsuchiya, Masayuki ; Ebisudani, Toshiki ; Sugimoto, Shinya ; Sato, Toshiro ; Yasuda, Hiroyuki ; Fukunaga, Koichi ; Sawada, Akihito ; Nemoto, Naoto ; Murata, Kazuyoshi ; Morimoto, Takuya ; Katayama, Kazuhiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c704t-d94acc3ed7cf35339acbcb166829697fff46559088602a5d9ef07dcd768b49ac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alveoli</topic><topic>Animal models</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Antiviral agents</topic><topic>Biology and life 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| identifier | ISSN: 1553-7374 |
| ispartof | PLoS pathogens, 2021-10, Vol.17 (10), p.e1009542-e1009542 |
| issn | 1553-7374 1553-7366 1553-7374 |
| language | eng |
| recordid | cdi_plos_journals_2598100896 |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Public Library of Science (PLoS); PubMed Central |
| subjects | Alveoli Animal models Antibodies Antigens Antiviral agents Biology and life sciences Candidates Coronaviruses COVID-19 Cytokines Dosage and administration Drug development Drug dosages Electron microscopy Enzymes Experiments Hamsters Infections Interferometry Intranasal medication Lungs Medicine and health sciences Membrane fusion Monoclonal antibodies Nanobodies Organoids Progeny Proteins Research and Analysis Methods Respiratory syncytial virus Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Signs and symptoms Testing Vaccines Viral antibodies Viral diseases Virus attachment Viruses Weight loss |
| title | Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T07%3A08%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Nasal%20delivery%20of%20single-domain%20antibody%20improves%20symptoms%20of%20SARS-CoV-2%20infection%20in%20an%20animal%20model&rft.jtitle=PLoS%20pathogens&rft.au=Haga,%20Kei&rft.date=2021-10-14&rft.volume=17&rft.issue=10&rft.spage=e1009542&rft.epage=e1009542&rft.pages=e1009542-e1009542&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1009542&rft_dat=%3Cgale_plos_%3EA681018344%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2598100896&rft_id=info:pmid/34648602&rft_galeid=A681018344&rft_doaj_id=oai_doaj_org_article_977c1f70bb2049c3a2f6faef7c65e0e7&rfr_iscdi=true |