Soloxolone Methyl Inhibits Influenza Virus Replication and Reduces Virus-induced Lung Inflammation

Overview

Journal Sci Rep

Specialty Science

Date 2017 Oct 27

PMID 29070858

Citations 10

Authors

Andrey V Markov

Alexandra V Senkova

Dawid Warszycki

Oksana V Salomatina

Nariman F Salakhutdinov

Marina A Zenkova

Evgeniya B Logashenko

Affiliations

Soon will be listed here.

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.

Citing Articles

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Savin I, Senkova A, Goncharova E, Zenkova M, Markov A Int J Mol Sci. 2024; 25(22).

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Evaluation of mycotoxins, mycobiota and toxigenic fungi in the traditional medicine .

Hu M, Wang L, Su D, Yuan Q, Xiao C, Guo L Front Microbiol. 2024; 15:1454683.

PMID: 39372267 PMC: 11452847. DOI: 10.3389/fmicb.2024.1454683.

Soloxolone methyl induces apoptosis and oxidative/ER stress in breast cancer cells and target cancer stem cell population.

Erturk E, Akgun O, Yildiz Y, Alper Kalkan P, Salomatina O, Salakhutdinov N Turk J Biol. 2023; 47(4):247-261.

PMID: 38152618 PMC: 10751089. DOI: 10.55730/1300-0152.2660.

Novel Epoxides of Soloxolone Methyl: An Effect of the Formation of Oxirane Ring and Stereoisomerism on Cytotoxic Profile, Anti-Metastatic and Anti-Inflammatory Activities In Vitro and In Vivo.

Salomatina O, Senkova A, Moralev A, Savin I, Komarova N, Salakhutdinov N Int J Mol Sci. 2022; 23(11).

PMID: 35682893 PMC: 9181525. DOI: 10.3390/ijms23116214.

Core genes involved in the regulation of acute lung injury and their association with COVID-19 and tumor progression: A bioinformatics and experimental study.

Senkova A, Savin I, Brenner E, Zenkova M, Markov A PLoS One. 2021; 16(11):e0260450.

PMID: 34807957 PMC: 8608348. DOI: 10.1371/journal.pone.0260450.

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