Preliminary Study On Antiviral Activity Of Berberine Derivate HB-13 Against Herpes Simplex Virus And Its Mechanisms Of Action

The diseases infected by herpes simplex virus (HSV-1 and HSV-2) are very common. They can result in many complications in the patients whose immune function is damaged. The prevalence of serum antibody to HSV-1 is more than 90% in common populations, and the prevalence of antibody to HSV-2 in different populations ranges from 4% to 60%. HSV-1 can cause many conditions including the common cold sore, herpetic keratitis and encephalitis, which may lead the cornea muddy or loss of sight, even death. And HSV-2 can cause genital herpes, which can transmit from mother to fetus and result in abortion or fetal abnormality. Both HSV-1 and HSV-2 may develop latent infection and reactivation response to various types of physiologic stress. At present, most of the treatment for HSV is based on aciclovir and ACV-related nucleoside analogues, all targeted against viral DNA synthesis, have been licensed for human use. There are still relatively minor problems about drug resistance among immunocompetent patients. However, among immunocompromised and allogeneic bone marrow transplantation patients the incidence of resistant HSV isolates is increasing, which is one of the main reasons for the continuous search of novel anti-HSV agents. HB-13 was an active compound from berberine(Bo) derivatives, and our previous screening studies showed that it had a strong anti-HSV-1 and anti-HSV-2 activity in vitro. In the present report, we have firstly investigated antiviral activity of HB-13 against HSV in vitro and in vivo, and then tried to find out its mechanisms of action underlying those involving in killing virus outside Vero cells, viral adsorption, release, DNA replication, protein synthesis and morphological changes. The paper consists of three chapters.Chapter I Antiviral activity of HB-13 and B₀ against HSV in vitroThe anti-HSV activity and relative 50% inhibiting concentration (IC50) of HB-13,B₀ and ACV were evaluated by inhibition of viral cytopathic effects at anon-cytotoxic concentration of the compounds. The results showed that 50% toxicityconcentration (TC50) of HB-13, B₀ and ACV aganist Vero cells was 27.11μg/ml,...