In vitro anti-influenza virus activity of synthetic humate analogues derived from protocatechuic acid

Two humic-like substances, the oxidative polymer of protocatechuic acid (OP-PCA) and humic acid inhibit the in vitro replication of influenza virus A/WSN/33 (H1N1) in Madin-Darby canine kidney (MDCK) cells at concentrations of no cytotoxicity. The 50% inhibitory concentration (IC50) for OP-PCA was 6.59+/-1.02 mug/ml when the compound was added at the stage of viral adsorption. When OP-PCA was added after virus adsorption, the IC50 was 53.27+/-12 mug/ml. The IC50 for humic acid was 48.61+/-7.32 mug/ml and 55.27+/-5.46 mug/ml respectively when the compound was added at the stage of viral adsorption or post-adsorption. In spite of structural resemblance of these two compounds, they exhibit different actions of anti-flu. The OP-PCA inhibits virus-induced hemagglutination and low pH-induced cell-cell fusion. Humic acid inhibits the endonuclease activity of viral RNA polymerase. The monomer of PCA shows no inhibition on influenza virus replication.