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

Summary.

 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 µg/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 ± 8.12 µg/ml. The IC₅₀ for humic acid was 48.61 ± 7.32 µg/ml and 55.27 ± 5.46 µg/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 endo-nuclease activity of viral RNA polymerase. The monomer of PCA shows no inhibition on influenza virus replication.