proportion of pandemic H1N1 (pH1N1) has declined subsequently, nevertheless 81,115 positive cases were reported from India (2017 to date). The emergence of resistance to drugs like tamiflu, designed against neuraminidase (a surface epitope of IAV), underscores the importance of assessing the antiviral property of alternative scaffolds such as substituted chalcones, aurones, quinolones etc which are non-analogous to sialic acid which is the endogenous target of neuraminidase, based on virtual screening against pH1N1. These scaffolds have alternate mechanism of binding i.e. they bind to the 430-loop (adjacent to the active site) of the active cavity.Methods & Materials: Screening of pH1N1 in severe acute respiratory illness cases referred from hospitals in Kolkata, WB during 2017-2019 was done by real-time PCR followed by sequencing of hemaglutinin (HA) and neuraminidase (NA) genes. Positive samples were cultured to isolate viruses. Antiviral activity of each of the scaffolds were assessed on pH1N1 circulating strains taking Tamiflu as positive control by HA titre and Crystal violet (CV) assay followed by their neuraminidase inhibition assay and enzyme kinetics.Results: Prevalence of pH1N1 was around 16.5% (n = 4106) with predominance in age groups <10 years and >50 years. No significant pattern of seasonality was observed. HA and CV assays revealed antiviral activity of some of the synthetic analogues. Effective concentrations [EC 50 ] ranging from 4 to 39 nM while NA inhibition assay showed its inhibitory concentrations [IC 50 ] around 17.6 M. NA enzyme-kinetic assay showed non-competitive inhibition of NA suggesting alternate mode of antiviral action.Conclusion: Subset of synthetic analogues revealed significant anti-influenza activity at non-toxic concentrations. The antiviral effects of these scaffolds were not due to Neuraminidase activity. Further experiments are underway to explore mechanism behind antiviral action.
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