Effect of cantharidin, cephalotaxine and homoharringtonine on "in vitro" models of hepatitis B virus (HBV) and bovine viral diarrhoea virus (BVDV) replication.

The effect as antiviral agents versus viral hepatitis B and C of three compounds purified from natural products commonly used as remedies in traditional Chinese medicine, cantharidin, cephalotaxine and homoharingtonine, was investigated. To assess the activity of these compounds against flavivirus, we used bovine viral diarrhoea virus (BVDV) as a surrogate for hepatitis C virus (HCV). Anti-BVDV activity was determined by reduction in BVDV-RNA production and protection of infected embryonic bovine trachea (EBTr) cells against the cytopathic effect of BVDV. The effect versus hepatitis B virus (HBV) was investigated by measuring HBsAg and HBV-DNA release from hepatoblastoma HepG2 2.2.15 cells infected with HBV. As positive control we used the standard anti-HBV and anti-HCV drugs, lamivudine and ribavirin, respectively. Up to 100 microM lamivudine and ribavirin did not induce cell toxicity, whereas they induced dose-dependent anti-HBV and anti-BVDV effects, respectively. In the same range, cantharidin, cephalotaxine and homoharringtonine induced toxicity in EBTr cells and had no protective effect against BVDV. In contrast, they were able to inhibit HBV production at concentrations 10- to 100-fold lower than those inducing cell toxicity, which suggests that they are useless for the treatment of infection by flaviviruses, but potentially useful in combined therapy against hepatitis B.