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Combination therapy protects macaques against advanced Marburg virus disease

Monoclonal antibodies (mAbs) and remdesivir, a small-molecule antiviral, are promising monotherapies for many viruses, including members of the genera Marburgvirus and Ebolavirus (family Filoviridae), and more recently, SARS-CoV-2. One of the major challenges of acute viral infections is the treatme...

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Autores principales: Cross, Robert W., Bornholdt, Zachary A., Prasad, Abhishek N., Borisevich, Viktoriya, Agans, Krystle N., Deer, Daniel J., Abelson, Dafna M., Kim, Do H., Shestowsky, William S., Campbell, Lioudmila A., Bunyan, Elaine, Geisbert, Joan B., Fenton, Karla A., Zeitlin, Larry, Porter, Danielle P., Geisbert, Thomas W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994808/
https://www.ncbi.nlm.nih.gov/pubmed/33767178
http://dx.doi.org/10.1038/s41467-021-22132-0
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author Cross, Robert W.
Bornholdt, Zachary A.
Prasad, Abhishek N.
Borisevich, Viktoriya
Agans, Krystle N.
Deer, Daniel J.
Abelson, Dafna M.
Kim, Do H.
Shestowsky, William S.
Campbell, Lioudmila A.
Bunyan, Elaine
Geisbert, Joan B.
Fenton, Karla A.
Zeitlin, Larry
Porter, Danielle P.
Geisbert, Thomas W.
author_facet Cross, Robert W.
Bornholdt, Zachary A.
Prasad, Abhishek N.
Borisevich, Viktoriya
Agans, Krystle N.
Deer, Daniel J.
Abelson, Dafna M.
Kim, Do H.
Shestowsky, William S.
Campbell, Lioudmila A.
Bunyan, Elaine
Geisbert, Joan B.
Fenton, Karla A.
Zeitlin, Larry
Porter, Danielle P.
Geisbert, Thomas W.
author_sort Cross, Robert W.
collection PubMed
description Monoclonal antibodies (mAbs) and remdesivir, a small-molecule antiviral, are promising monotherapies for many viruses, including members of the genera Marburgvirus and Ebolavirus (family Filoviridae), and more recently, SARS-CoV-2. One of the major challenges of acute viral infections is the treatment of advanced disease. Thus, extending the window of therapeutic intervention is critical. Here, we explore the benefit of combination therapy with a mAb and remdesivir in a non-human primate model of Marburg virus (MARV) disease. While rhesus monkeys are protected against lethal infection when treatment with either a human mAb (MR186-YTE; 100%), or remdesivir (80%), is initiated 5 days post-inoculation (dpi) with MARV, no animals survive when either treatment is initiated alone beginning 6 dpi. However, by combining MR186-YTE with remdesivir beginning 6 dpi, significant protection (80%) is achieved, thereby extending the therapeutic window. These results suggest value in exploring combination therapy in patients presenting with advanced filovirus disease.
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spelling pubmed-79948082021-04-16 Combination therapy protects macaques against advanced Marburg virus disease Cross, Robert W. Bornholdt, Zachary A. Prasad, Abhishek N. Borisevich, Viktoriya Agans, Krystle N. Deer, Daniel J. Abelson, Dafna M. Kim, Do H. Shestowsky, William S. Campbell, Lioudmila A. Bunyan, Elaine Geisbert, Joan B. Fenton, Karla A. Zeitlin, Larry Porter, Danielle P. Geisbert, Thomas W. Nat Commun Article Monoclonal antibodies (mAbs) and remdesivir, a small-molecule antiviral, are promising monotherapies for many viruses, including members of the genera Marburgvirus and Ebolavirus (family Filoviridae), and more recently, SARS-CoV-2. One of the major challenges of acute viral infections is the treatment of advanced disease. Thus, extending the window of therapeutic intervention is critical. Here, we explore the benefit of combination therapy with a mAb and remdesivir in a non-human primate model of Marburg virus (MARV) disease. While rhesus monkeys are protected against lethal infection when treatment with either a human mAb (MR186-YTE; 100%), or remdesivir (80%), is initiated 5 days post-inoculation (dpi) with MARV, no animals survive when either treatment is initiated alone beginning 6 dpi. However, by combining MR186-YTE with remdesivir beginning 6 dpi, significant protection (80%) is achieved, thereby extending the therapeutic window. These results suggest value in exploring combination therapy in patients presenting with advanced filovirus disease. Nature Publishing Group UK 2021-03-25 /pmc/articles/PMC7994808/ /pubmed/33767178 http://dx.doi.org/10.1038/s41467-021-22132-0 Text en © The Author(s) 2021 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/.
spellingShingle Article
Cross, Robert W.
Bornholdt, Zachary A.
Prasad, Abhishek N.
Borisevich, Viktoriya
Agans, Krystle N.
Deer, Daniel J.
Abelson, Dafna M.
Kim, Do H.
Shestowsky, William S.
Campbell, Lioudmila A.
Bunyan, Elaine
Geisbert, Joan B.
Fenton, Karla A.
Zeitlin, Larry
Porter, Danielle P.
Geisbert, Thomas W.
Combination therapy protects macaques against advanced Marburg virus disease
title Combination therapy protects macaques against advanced Marburg virus disease
title_full Combination therapy protects macaques against advanced Marburg virus disease
title_fullStr Combination therapy protects macaques against advanced Marburg virus disease
title_full_unstemmed Combination therapy protects macaques against advanced Marburg virus disease
title_short Combination therapy protects macaques against advanced Marburg virus disease
title_sort combination therapy protects macaques against advanced marburg virus disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994808/
https://www.ncbi.nlm.nih.gov/pubmed/33767178
http://dx.doi.org/10.1038/s41467-021-22132-0
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