The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern

There is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a potent inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally and that is in clinical development. We here report that PF-332 exerts equipotent in vitro acti...

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Autores principales: Abdelnabi, Rana, Foo, Caroline S., Jochmans, Dirk, Vangeel, Laura, De Jonghe, Steven, Augustijns, Patrick, Mols, Raf, Weynand, Birgit, Wattanakul, Thanaporn, Hoglund, Richard M., Tarning, Joel, Mowbray, Charles E., Sjö, Peter, Escudié, Fanny, Scandale, Ivan, Chatelain, Eric, Neyts, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847371/
https://www.ncbi.nlm.nih.gov/pubmed/35169114
http://dx.doi.org/10.1038/s41467-022-28354-0
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author Abdelnabi, Rana
Foo, Caroline S.
Jochmans, Dirk
Vangeel, Laura
De Jonghe, Steven
Augustijns, Patrick
Mols, Raf
Weynand, Birgit
Wattanakul, Thanaporn
Hoglund, Richard M.
Tarning, Joel
Mowbray, Charles E.
Sjö, Peter
Escudié, Fanny
Scandale, Ivan
Chatelain, Eric
Neyts, Johan
author_facet Abdelnabi, Rana
Foo, Caroline S.
Jochmans, Dirk
Vangeel, Laura
De Jonghe, Steven
Augustijns, Patrick
Mols, Raf
Weynand, Birgit
Wattanakul, Thanaporn
Hoglund, Richard M.
Tarning, Joel
Mowbray, Charles E.
Sjö, Peter
Escudié, Fanny
Scandale, Ivan
Chatelain, Eric
Neyts, Johan
author_sort Abdelnabi, Rana
collection PubMed
description There is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a potent inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally and that is in clinical development. We here report that PF-332 exerts equipotent in vitro activity against the four SARS-CoV-2 variants of concerns (VoC) and that it can completely arrest replication of the alpha variant in primary human airway epithelial cells grown at the air-liquid interface. Treatment of Syrian Golden hamsters with PF-332 (250 mg/kg, twice daily) completely protected the animals against intranasal infection with the beta (B.1.351) and delta (B.1.617.2) SARS-CoV-2 variants. Moreover, treatment of SARS-CoV-2 (B.1.617.2) infected animals with PF-332 completely prevented transmission to untreated co-housed sentinels.
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spelling pubmed-88473712022-03-04 The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern Abdelnabi, Rana Foo, Caroline S. Jochmans, Dirk Vangeel, Laura De Jonghe, Steven Augustijns, Patrick Mols, Raf Weynand, Birgit Wattanakul, Thanaporn Hoglund, Richard M. Tarning, Joel Mowbray, Charles E. Sjö, Peter Escudié, Fanny Scandale, Ivan Chatelain, Eric Neyts, Johan Nat Commun Article There is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a potent inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally and that is in clinical development. We here report that PF-332 exerts equipotent in vitro activity against the four SARS-CoV-2 variants of concerns (VoC) and that it can completely arrest replication of the alpha variant in primary human airway epithelial cells grown at the air-liquid interface. Treatment of Syrian Golden hamsters with PF-332 (250 mg/kg, twice daily) completely protected the animals against intranasal infection with the beta (B.1.351) and delta (B.1.617.2) SARS-CoV-2 variants. Moreover, treatment of SARS-CoV-2 (B.1.617.2) infected animals with PF-332 completely prevented transmission to untreated co-housed sentinels. Nature Publishing Group UK 2022-02-15 /pmc/articles/PMC8847371/ /pubmed/35169114 http://dx.doi.org/10.1038/s41467-022-28354-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Abdelnabi, Rana
Foo, Caroline S.
Jochmans, Dirk
Vangeel, Laura
De Jonghe, Steven
Augustijns, Patrick
Mols, Raf
Weynand, Birgit
Wattanakul, Thanaporn
Hoglund, Richard M.
Tarning, Joel
Mowbray, Charles E.
Sjö, Peter
Escudié, Fanny
Scandale, Ivan
Chatelain, Eric
Neyts, Johan
The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
title The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
title_full The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
title_fullStr The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
title_full_unstemmed The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
title_short The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern
title_sort oral protease inhibitor (pf-07321332) protects syrian hamsters against infection with sars-cov-2 variants of concern
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847371/
https://www.ncbi.nlm.nih.gov/pubmed/35169114
http://dx.doi.org/10.1038/s41467-022-28354-0
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