A novel aqueous extract from rice fermented with Aspergillus oryzae and Saccharomyces cerevisiae possesses an anti-influenza A virus activity

Human influenza virus infections occur annually worldwide and are associated with high morbidity and mortality. Hence, development of novel anti-influenza drugs is urgently required. Rice Power® extract developed by the Yushin Brewer Co. Ltd. is a novel aqueous extract of rice obtained via saccharization and fermentation with various microorganisms, such as Aspergillus oryzae, yeast [such as Saccharomyces cerevisiae], and lactic acid bacteria, possessing various biological and pharmacological properties. In our previous experimental screening with thirty types of Rice Power® extracts, we observed that the 30th Rice Power® (Y30) extract promoted the survival of influenza A virus-infected Madin-Darby canine kidney (MDCK) cells. Therefore, to identify compounds for the development of novel anti-influenza drugs, we aimed to investigate whether the Y30 extract exhibits anti-influenza A virus activity. In the present study, we demonstrated that the Y30 extract strongly promoted the survival of influenza A H1N1 Puerto Rico 8/34 (A/PR/8/34), California 7/09, or H3N2 Aichi 2/68 (A/Aichi/2/68) viruses-infected MDCK cells and inhibited A/PR/8/34 or A/Aichi/2/68 viruses infection and growth in the co-treatment and pre-infection experiments. The pre-treatment of Y30 extract on MDCK cells did not induce anti-influenza activity in the cell. The Y30 extract did not significantly affect influenza A virus hemagglutination, and neuraminidase and RNA-dependent RNA polymerase activities. Interestingly, the electron microscopy experiment revealed that the Y30 extract disrupts the integrity of influenza A virus particles by permeabilizing the viral membrane envelope, suggesting that Y30 extract has a direct virucidal effect against influenza A virus. Furthermore, we observed that compared to the ethyl acetate (EtOAc) extract, the water extract of Y30 extract considerably promoted the survival of cells infected with A/PR/8/34 virus. These results indicated that more anti-influenza components were present in the water extract of Y30 extract than in the EtOAc extract. Our results highlight the potential of a rice extract fermented with A. oryzae and S. cerevisiae as an anti-influenza medicine and a drug source for the development of anti-influenza compounds.

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Comprehensive N ‐glycosylation analysis of the influenza A virus proteins HA and NA from adherent and suspension MDCK cells

FEBS Journal ◽

10.1111/febs.15787 ◽

2021 ◽

Author(s):

Alexander Pralow ◽

Marcus Hoffmann ◽

Terry Nguyen‐Khuong ◽

Markus Pioch ◽

René Hennig ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Mdck Cells ◽

Virus Proteins

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A human cell polarity protein Lgl2 regulates influenza A virus nucleoprotein exportation from nucleus in MDCK cells

Journal of Biosciences ◽

10.1007/s12038-020-00039-0 ◽

2020 ◽

Vol 45 (1) ◽

Author(s):

Jing Liu ◽

Haiying Wang ◽

Mengdan Fang ◽

Xuexin Chen ◽

Xiaobo Zeng

Keyword(s):

Cell Polarity ◽

Influenza A Virus ◽

Human Cell ◽

Influenza A ◽

Mdck Cells

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Use of electric cell-substrate impedance sensing as a tool for quantifying cytopathic effect in influenza A virus infected MDCK cells in real-time

Journal of Virological Methods ◽

10.1016/j.jviromet.2005.06.023 ◽

2005 ◽

Vol 130 (1-2) ◽

pp. 157-161 ◽

Cited By ~ 51

Author(s):

Morgan H. McCoy ◽

Eugenia Wang

Keyword(s):

Real Time ◽

Influenza A Virus ◽

Influenza A ◽

Cytopathic Effect ◽

Mdck Cells ◽

Impedance Sensing ◽

Cell Substrate

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The seafood Musculus senhousei shows anti-influenza A virus activity by targeting virion envelope lipids

Biochemical Pharmacology ◽

10.1016/j.bcp.2020.113982 ◽

2020 ◽

Vol 177 ◽

pp. 113982 ◽

Cited By ~ 1

Author(s):

Daiwei Chen ◽

Shengsheng Lu ◽

Guang Yang ◽

Xiaoyan Pan ◽

Sheng Fan ◽

...

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Virus Activity ◽

Virion Envelope

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In vivo anti-influenza A virus activity of antisense oligonucleotides

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)41254-7 ◽

1998 ◽

Vol 76 ◽

pp. 286

Author(s):

Tadashi Mizuta ◽

Masatoshi Fujiwara ◽

Tomoyuki Yokota ◽

Shiro Shigeta ◽

Toshifumi Hatta ◽

...

Keyword(s):

Influenza A Virus ◽

Antisense Oligonucleotides ◽

Influenza A ◽

Virus Activity

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Ceramide Suppresses Influenza A Virus Replication In Vitro

Journal of Virology ◽

10.1128/jvi.00053-19 ◽

2019 ◽

Vol 93 (7) ◽

Cited By ~ 8

Author(s):

Nadia Soudani ◽

Rouba Hage-Sleiman ◽

Walid Karam ◽

Ghassan Dbaibo ◽

Hassan Zaraket

Keyword(s):

Influenza A Virus ◽

Virus Replication ◽

Influenza A ◽

De Novo ◽

Dependent Manner ◽

Biosynthesis Pathway ◽

Influenza A H1n1 ◽

Ceramide Accumulation ◽

Antiviral Role

ABSTRACT Annual influenza outbreaks are associated with significant morbidity and mortality worldwide despite the availability of seasonal vaccines. Influenza pathogenesis depends on the manipulation of host cell signaling to promote virus replication. Ceramide is a sphingosine-derived lipid that regulates diverse cellular processes. Studies highlighted the differential role of ceramide de novo biosynthesis on the propagation of various viruses. Whether ceramide plays, a role in influenza virus replication is not known. In this study, we assessed the potential interplay between the influenza A (IAV) and ceramide biosynthesis pathways. The accumulation of ceramide in human lung epithelial cells infected with influenza A/H1N1 virus strains was evaluated using thin-layer chromatography and/or confocal microscopy. Virus replication was assessed upon the regulation of the de novo ceramide biosynthesis pathway. A significant increase in ceramide accumulation was observed in cells infected with IAV in a dose- and time-dependent manner. Inoculating the cells with UV-inactivated IAV did not result in ceramide accumulation in the cells, suggesting that the induction of ceramide required an active virus replication. Inhibiting de novo ceramide significantly decreased ceramide accumulation and enhanced virus replication. The addition of exogenous C6-ceramide prior to infection mediated an increase in cellular ceramide levels and significantly attenuated IAV replication and reduced viral titers (≈1 log10 PFU/ml unit). Therefore, our data demonstrate that ceramide accumulation through de novo biosynthesis pathway plays a protective and antiviral role against IAV infection. These findings propose new avenues for development of antiviral molecules and strategies. IMPORTANCE Understanding the effect of sphingolipid metabolism on viral pathogenesis provide important insights into the development of therapeutic strategies against microbial infections. In this study, we demonstrate a critical role of ceramide during influenza A virus infection. We demonstrate that ceramide produced through de novo biosynthesis possess an antiviral role. These observations unlock new opportunities for the development of novel antiviral therapies against influenza.

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Long-Lasting Mucosal and Systemic Immunity against Influenza A Virus Is Significantly Prolonged and Protective by Nasal Whole Influenza Immunization with Mucosal Adjuvant N3 and DNA-Plasmid Expressing Flagellin in Aging In- and Outbred Mice

Vaccines ◽

10.3390/vaccines7030064 ◽

2019 ◽

Vol 7 (3) ◽

pp. 64 ◽

Cited By ~ 2

Author(s):

Jorma Hinkula ◽

Sanna Nyström ◽

Claudia Devito ◽

Andreas Bråve ◽

Steven E. Applequist

Keyword(s):

Immune Responses ◽

Influenza A Virus ◽

Influenza A ◽

Influenza Infection ◽

Inbred Mouse ◽

Herd Immunity ◽

Serum Antibody ◽

Mouse Strains ◽

Virus Challenge ◽

Influenza A H1n1

Background: Vaccination is commonly used to prevent and control influenza infection in humans. However, improvements in the ease of delivery and strength of immunogenicity could markedly improve herd immunity. The aim of this pre-clinical study is to test the potential improvements to existing intranasal delivery of formalin-inactivated whole Influenza A vaccines (WIV) by formulation with a cationic lipid-based adjuvant (N3). Additionally, we combined WIV and N3 with a DNA-encoded TLR5 agonist secreted flagellin (pFliC(-gly)) as an adjuvant, as this adjuvant has previously been shown to improve the effectiveness of plasmid-encoded DNA antigens. Methods: Outbred and inbred mouse strains were intranasally immunized with unadjuvanted WIV A/H1N1/SI 2006 or WIV that was formulated with N3 alone. Additional groups were immunized with WIV and N3 adjuvant combined with pFliC(-gly). Homo and heterotypic humoral anti-WIV immune responses were assayed from serum and lung by ELISA and hemagglutination inhibition assay. Homo and heterotypic cellular immune responses to WIV and Influenza A NP were also determined. Results: WIV combined with N3 lipid adjuvant the pFliC(-gly) significantly increased homotypic influenza specific serum antibody responses (>200-fold), increased the IgG2 responses, indicating a mixed Th1/Th2-type immunity, and increased the HAI-titer (>100-fold). Enhanced cell-mediated IFNγ secreting influenza directed CD4+ and CD8+ T cell responses (>40-fold) to homotypic and heterosubtypic influenza A virus and peptides. Long-term and protective immunity was obtained. Conclusions: These results indicate that inactivated influenza virus that was formulated with N3 cationic adjuvant significantly enhanced broad systemic and mucosal influenza specific immune responses. These responses were broadened and further increased by incorporating DNA plasmids encoding FliC from S. typhimurum as an adjuvant providing long lasting protection against heterologous Influenza A/H1N1/CA09pdm virus challenge.

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