Effects of the combination of baicalin and ribavirin on influenza A virus infection in vitro and in vivo

Aim To evaluate effects of the combination of baicalin and ribavirin on influenza A virus infection in cell culture and in mice,and provide experimental basis for their co-use clinically.Methods MTT and CPE assays were applied to test protective effects of baicalin and ribavirin against three different influenza virus subtypes in MDCK cells under the condition of used alone or in combination,respectively.CI analysis and MacSynergyⅡ analysis were applied to analyze interaction of baicalin and ribavirin in vitro,respectively.Neuraminidase inhibition assay was used to evaluate inhibitory effects of baicalin on the activity of influenza viral neuraminidases.The BALB/c mice infected with H1N1 virus were adopted to test protective effects of baicalin and ribavirin used alone or in combination.Results The combination of baicalin and ribavirin exhibited additive inhibitory activities against H5N1 and H1N1 viruses,and significant synergistic inhibitory activity against H9N2 virus in cell culture.The 50% effective inhibitory concentrations(IC50) of baicalin on the NAs from three different viruses ranged from 0.29 to 0.49 mmol·L-1.The treatment of ribavirin plus baicalin significantly improved survival rates and surviving times of mice infected with H1N1 virus,when compared with the treatment of either compound used alone.Conclusion Baicalin has some inhibitory effect on influenza viral neuraminidases.The combination of baicalin and ribavirin shows additive or synergistic inhibitory activity against different influenza viruses in vitro,depending on the tested virus subtypes.The treatment of ribavirin plus baicalin was more effective in influenza A infection in mice than either compound used alone.