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

Journal Scientific Reports
ISSN: 2045-2322
Output data Year: 2017, Volume: 7, Article number : 13968, Pages count : DOI: 10.1038/s41598-017-14029-0
Authors Markov Andrey V. 1 , Sen'kova Alexandra V. 1 , Warszycki Dawid 2 , Salomatina Oksana V. 3 , Salakhutdinov Nariman F. 3 , Zenkova Marina A. 1 , Logashenko Evgeniya B. 1
Affiliations
1 (Данные Web of science) Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, 8 Lavrentev Ave, Novosibirsk 630090, Russia
2 (Данные Web of science) Polish Acad Sci, Inst Pharmacol, 12 Smetna St, PL-31343 Krakow, Poland
3 (Данные Web of science) Russian Acad Sci, Siberian Branch, NN Vorozhtsov Novosibirsk Inst Organ Chem, 9 Lavrentev Ave, Novosibirsk 630090, Russia

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-18 beta H-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-alpha. 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.
Cite: Markov A.V. , Sen'kova A.V. , Warszycki D. , Salomatina O.V. , Salakhutdinov N.F. , Zenkova M.A. , Logashenko E.B.
Soloxolone methyl inhibits influenza virus replication and reduces virus-induced lung inflammation
Scientific Reports. 2017. V.7. 13968 . DOI: 10.1038/s41598-017-14029-0 WOS Scopus РИНЦ OpenAlex
Files: Full text from publisher
Dates:
Published online: Oct 25, 2017
Published print: Dec 1, 2017
Identifiers:
Web of science: WOS:000413700200007
Scopus: 2-s2.0-85032225854
Elibrary: 31127144
OpenAlex: W2765771667
Citing:
DB Citing
Web of science 24
Scopus 25
Elibrary 26
OpenAlex 28
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