Antiviral activity of baicalin against influenza virus H1N1-pdm09 is due to modulation of NS1-mediated cellular innate immune responses

Nayak, Malabika; Agrawal, Anurodh Shankar; Bose, Sudeshna; Naskar, Shaon; Bhowmick, Rahul; Chakrabarti, Saikat; Sarkar, Sagartirtha; Chawla‐Sarkar, Mamta

doi:10.1093/jac/dkt534

Cited by 107 publications

(81 citation statements)

References 70 publications

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“…Baicalin was able to induce the production of interferon-gamma (IFN-ɣ) in natural killer (NK), CD4+ and CD8+ T cells during in vitro influenza A virus infection. It was suggested that baicalin was able to directly bind NS1-p85β (RNA binding domain), which was the main mediator to downregulate IFN-ɣ [15]. The induction of IFN-ɣ triggered the immune system to activate the Janus kinase/signal transducer and activator of transcription protein 1 (JAK/STAT1) pathway, which led to the expression of IFN-ɣinducible genes.…”

Section: Flavonoids Against Non-picornavirusesmentioning

confidence: 99%

Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Lalani

Poh

2020

Viruses

159

101

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Flavonoids are natural biomolecules that are known to be effective antivirals. These biomolecules can act at different stages of viral infection, particularly at the molecular level to inhibit viral growth. Enterovirus A71 (EV-A71), a non-enveloped RNA virus, is one of the causative agents of hand, foot and mouth disease (HFMD), which is prevalent in Asia. Despite much effort, no clinically approved antiviral treatment is available for children suffering from HFMD. Flavonoids from plants serve as a vast reservoir of therapeutically active constituents that have been explored as potential antiviral candidates against RNA and DNA viruses. Here, we reviewed flavonoids as evidence-based natural sources of antivirals against non-picornaviruses and picornaviruses. The detailed molecular mechanisms involved in the inhibition of EV-A71 infections are discussed.

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Section: Flavonoids Against Non-picornavirusesmentioning

confidence: 99%

Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Lalani

Poh

2020

Viruses

159

101

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“…The NS1 protein has been identified as a potential drug target (Maroto, Fernandez et al 2008;Basu, Walkiewicz et al 2009;Jablonski, Basu et al;Walkiewicz, Basu et al 2011). Previous studies on potential ligand binding sites in influenza NS1 identified 2 sites in the RNA binding domain that would interact with R35 or D39 (Darapaneni, Prabhaker et al 2009), and at least one potential drug, baicalin has been shown to interact with R35, R38, and D39 (Nayak, Agrawal et al 2014)…”

Section: Discussionmentioning

confidence: 99%

The R35 residue of the influenza A virus NS1 protein has minimal effects on nuclear localization but alters virus replication through disrupting protein dimerization

Lalime

Pekosz

2014

Virology

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The influenza A virus NS1 protein has a nuclear localization sequence (NLS) in the amino terminal region. This NLS overlaps sequences that are important for RNA binding as well as protein dimerization. To assess the significance of the NS1 NLS on influenza virus replication, the NLS amino acids were individually mutated to alanines and recombinant viruses encoding these mutations were rescued. Viruses containing NS1 proteins with mutations at R37, R38 and K41 displayed minimal changes in replication or NS1 protein nuclear localization. Recombinant viruses encoding NS1 R35A were not recovered but viruses containing second site mutations at position D39 in addition to the R35A mutation were isolated. The mutations at position 39 were shown to partially restore NS1 protein dimerization but had minimal effects on nuclear localization. These data indicate the amino acids in the NS1 NLS region play a more important role in protein dimerization compared to nuclear localization.

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“…Recent, studies have reported that baicalin regulates Toll-like receptors (TLRs) [15], NOD-like receptors (NODR) and other immune receptors in the innate and adaptive systems [16]. Previous studies have also suggested that LYSO can enhance the activity of some antibacterial drugs [17].…”

Section: Introductionmentioning

confidence: 99%

Baicalin promotes the bacteriostatic activity of lysozyme on S. aureus in mammary glands and neutrophilic granulocytes in mice

et al. 2017

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Staphylococcus aureus causes mastitis as a result of community-acquired or nosocomial infections. Lysozyme (LYSO) is an enzyme that is upregulated in many organisms during the innate immune response against infection by bacterial pathogens. Baicalin is a bioactive flavonoid that can bind to enzymes, often to potentiate their effect. Here we tested the effects of baicalin on the activity of LYSO using the S. aureus mastitis mouse model and neutrophilic granulocyte model of S. aureus infection. In our experiments, S. aureus counts decreased with increasing baicalin concentration. Furthermore, qPCR and western blot analyses showed that LYSO expression was unaffected by baicalin, while fluorescence quenching and UV fluorescence spectral analyses showed that baicalin binds to LYSO. To test whether this binding increased LYSO activity, we assessed LYSO-induced bacteriostasis in the presence of baicalin. Our results showed that LYSO-induced S. aureus bacteriostasis increased with increasing concentrations of baicalin, and that baicalin binding to LYSO synergistically increased the antibacterial activity of LYSO. These results demonstrate that baicalin enhances LYSO-induced bacteriostasis during the innate immune response to S. aureus. They suggest baicalin is a potentially useful therapeutic agent for the treatment of bacterial infections.

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Antiviral activity of baicalin against influenza virus H1N1-pdm09 is due to modulation of NS1-mediated cellular innate immune responses

Abstract: Overall, this study highlights that baicalin exerts its anti-influenza virus activity by modulating viral protein NS1, resulting in up-regulation of IFN-induced antiviral signalling and a decrease in PI3K/Akt signalling in cells.

Cited by 107 publications

References 70 publications

Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

The R35 residue of the influenza A virus NS1 protein has minimal effects on nuclear localization but alters virus replication through disrupting protein dimerization

Baicalin promotes the bacteriostatic activity of lysozyme on S. aureus in mammary glands and neutrophilic granulocytes in mice

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