Antiviral activity of baicalin against influenza virus H1N1 pdm09 is due to modulation of NS1-mediated cellular innate immune responses
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Antiviral activity of baicalin against influenza virus H1N1 pdm09 is due to modulation of NS1-mediated cellular innate immune responses
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| Creator |
Nayak, Mukti Kant
Agrawal, Anurodh S Bose, Sudeshna Naskar, Shaon Bhowmick, Rahul Chakrabarti, Saikat Sarkar, Sagartirtha Chawla-Sarkar, Mamta |
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| Subject |
Structural Biology & Bioinformatics
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| Description |
Baicalin, a flavonoid, has been shown to have antiviral and anti-inflammatory activities, although the mechanism of action has been unknown. Therefore, attempts were made to analyse the mechanism behind the antiviral effects of baicalin using an influenza A virus (IAV) model in vitro and in vivo.Baicalin’s anti-influenza activity was elucidated (in vitro and in vivo) utilizing pandemic influenza strain A/H1N1/Eastern India/66/pdm09 (H1N1-pdm09). Anti-influenza activity was measured by plaque inhibition, fluorescent focus-forming units (ffu) and quantifying viral transcripts using quantitative real-time PCR following treatment with baicalin in a dose- and time-dependent manner. The role of the IAV non-structural protein 1 (NS1) gene in modulating host responses was measured by immunoblotting, co-immunoprecipitation and molecular docking.Baicalin treatment following IAV infection revealed up-regulation of interferon (IFN)-induced antiviral signalling and decreased phosphoinositide 3-kinase/Akt (PI3K/Akt) activation compared with infected, untreated controls. Baicalin exerts its antiviral effects by modulating the function of the IAV-encoded NS1 protein. NS1 has been shown to counteract cellular antiviral responses by down-regulating IFN induction and up-regulating PI3K/ Akt signalling. Baicalin disrupted NS1–p85b binding. Molecular docking predicted the binding site of baicalin in the RNA binding domain (RBD) of NS1. Site-directed mutagenesis within the RBD region of NS1 and the difference in the fluorescence quenching pattern of full-length NS1 and mutant NS1 proteins in the presence of baicalin confirmed the interaction of baicalin with the NS1 RBD. Amino acid residues 39–43 of the NS1 RBD were
found to be crucial for the baicalin–NS1 interaction.
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.
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| Date |
2014
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2172/1/JOURNAL_OF_ANTIMICROBIAL_CHEMOTHERAPY__V_69_(_5_)_1298%2D1310_;2014[114].pdf
Nayak, Mukti Kant and Agrawal, Anurodh S and Bose, Sudeshna and Naskar, Shaon and Bhowmick, Rahul and Chakrabarti, Saikat and Sarkar, Sagartirtha and Chawla-Sarkar, Mamta (2014) Antiviral activity of baicalin against influenza virus H1N1 pdm09 is due to modulation of NS1-mediated cellular innate immune responses. Journal of Antimicrobial Chemotherapy, 69 (5). pp. 1298-1310. |
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| Relation |
http://dx.doi.org/10.1093/jac/dkt534
http://www.eprints.iicb.res.in/2172/ |
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