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The inhibitory effect of sodium baicalin on oseltamivir-resistant influenza A virus via reduction of neuraminidase activity.
Archives of Pharmacal Research 2018 June
Baicalin was identified as a neuraminidase (NA) inhibitor displaying anti-influenza A virus (IAV) activity. However, its poor solubility in saline has limited its use in the clinic. We generated sodium baicalin and showed that it exhibited greatly increased solubility in saline. Its efficacy against oseltamivir-resistant mutant A/FM/1/47-H275Y (H1N1-H275Y) was evaluated in vitro and in vivo. Results showed that 10 μM of sodium baicalin inhibited A/FM/1/47 (H1N1), A/Beijing/32/92 (H3N2) and H1N1-H275Y in MDCK cells in a dose-dependent manner, with inhibitory rates of 83.9, 75.9 and 47.7%, respectively. Intravenous administration of sodium baicalin at 100 mg/kg/d enabled the survival of 20% of H1N1-H275Y-infected mice. The treatment alleviated body weight loss and lung injury. Moreover, sodium baicalin exerted a clear inhibitory effect on NAs. The IC50 values of sodium baicalin against H1N1-H275Y and cells-expressing A/Anhui/1/2013-R294K (H7N9-R294K) NA protein (N9-R294K) were 214.4 μM and 216.3 μM. Direct interactions between sodium baicalin and NA were observed, and we simulated the interactions of sodium baicalin with N9-R294K and N9 near the active sites of OC-N9-R294K and OC-N9. The residues responsible for the sodium baicalin-N9-R294K and sodium baicalin-N9 interactions were the same, confirming that sodium baicalin exerts effects on wild-type and oseltamivir-resistant viral strains.
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