Soloxolone methyl inhibits influenza virus replication and reduces virus-induced lung inflammation

Abstract Highly pathogenic influenza viruses pose a serious public health threat to humans. Although vaccines are available, new antivirals are needed to efficiently control disease progression and virus transmission due to the emergence of drug-resistant viral strains. In this study, we describe th...

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Autores principales:	Andrey V. Markov, Alexandra V. Sen’kova, Dawid Warszycki, Oksana V. Salomatina, Nariman F. Salakhutdinov, Marina A. Zenkova, Evgeniya B. Logashenko
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ea4e8d5e87eb4582ac88be3f232b7d9f
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spelling	oai:doaj.org-article:ea4e8d5e87eb4582ac88be3f232b7d9f2021-12-02T11:41:00ZSoloxolone methyl inhibits influenza virus replication and reduces virus-induced lung inflammation10.1038/s41598-017-14029-02045-2322https://doaj.org/article/ea4e8d5e87eb4582ac88be3f232b7d9f2017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-14029-0https://doaj.org/toc/2045-2322Abstract Highly pathogenic influenza viruses pose a serious public health threat to humans. Although vaccines are available, new antivirals are needed to efficiently control disease progression and virus transmission due to the emergence of drug-resistant viral strains. In this study, we describe the anti-viral properties of Soloxolone methyl (SM) (methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate, a chemical derivative of glycyrrhetinic acid) against the flu virus. Anti-flu efficacy studies revealed that SM exhibits antiviral activity against the H1N1 influenza A virus in a dose-dependent manner causing a more than 10-fold decrease in virus titer and a reduction in the expression of NP and M2 viral proteins. In a time-of-addition study, SM was found to act at an early stage of infection to exhibit an inhibitory effect on both the attachment step and virus uptake into cells. Also, in infected cells SM downregulates the expression of the inflammatory cytokines IL-6 and TNF-α. In infected mice, SM administered intranasally prior to and after infection significantly decreases virus titers in the lung and prevents post-challenge pneumonia. Together, these results suggest that Soloxolone methyl might serve as an effective therapeutic agent to manage influenza outbreaks and virus-associated complications, and further preclinical and clinical investigation may be warranted.Andrey V. MarkovAlexandra V. Sen’kovaDawid WarszyckiOksana V. SalomatinaNariman F. SalakhutdinovMarina A. ZenkovaEvgeniya B. LogashenkoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrey V. Markov Alexandra V. Sen’kova Dawid Warszycki Oksana V. Salomatina Nariman F. Salakhutdinov Marina A. Zenkova Evgeniya B. Logashenko Soloxolone methyl inhibits influenza virus replication and reduces virus-induced lung inflammation
description	Abstract Highly pathogenic influenza viruses pose a serious public health threat to humans. Although vaccines are available, new antivirals are needed to efficiently control disease progression and virus transmission due to the emergence of drug-resistant viral strains. In this study, we describe the anti-viral properties of Soloxolone methyl (SM) (methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate, a chemical derivative of glycyrrhetinic acid) against the flu virus. Anti-flu efficacy studies revealed that SM exhibits antiviral activity against the H1N1 influenza A virus in a dose-dependent manner causing a more than 10-fold decrease in virus titer and a reduction in the expression of NP and M2 viral proteins. In a time-of-addition study, SM was found to act at an early stage of infection to exhibit an inhibitory effect on both the attachment step and virus uptake into cells. Also, in infected cells SM downregulates the expression of the inflammatory cytokines IL-6 and TNF-α. In infected mice, SM administered intranasally prior to and after infection significantly decreases virus titers in the lung and prevents post-challenge pneumonia. Together, these results suggest that Soloxolone methyl might serve as an effective therapeutic agent to manage influenza outbreaks and virus-associated complications, and further preclinical and clinical investigation may be warranted.
format	article
author	Andrey V. Markov Alexandra V. Sen’kova Dawid Warszycki Oksana V. Salomatina Nariman F. Salakhutdinov Marina A. Zenkova Evgeniya B. Logashenko
author_facet	Andrey V. Markov Alexandra V. Sen’kova Dawid Warszycki Oksana V. Salomatina Nariman F. Salakhutdinov Marina A. Zenkova Evgeniya B. Logashenko
author_sort	Andrey V. Markov
title	Soloxolone methyl inhibits influenza virus replication and reduces virus-induced lung inflammation
title_short	Soloxolone methyl inhibits influenza virus replication and reduces virus-induced lung inflammation
title_full	Soloxolone methyl inhibits influenza virus replication and reduces virus-induced lung inflammation
title_fullStr	Soloxolone methyl inhibits influenza virus replication and reduces virus-induced lung inflammation
title_full_unstemmed	Soloxolone methyl inhibits influenza virus replication and reduces virus-induced lung inflammation
title_sort	soloxolone methyl inhibits influenza virus replication and reduces virus-induced lung inflammation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ea4e8d5e87eb4582ac88be3f232b7d9f
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Soloxolone methyl inhibits influenza virus replication and reduces virus-induced lung inflammation

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