Study On Inhibition Of Herpes Simplex Virus Type 1 Replication In Vitro And In Vivo And Brain Protection Against Infection In Mice By New Antibiotics S632A₃

HSV has been considered to be one of most common pathogen in human being because it can cause many herpetic diseases and is associated with such cancer as cheilocarcinoma, cervical carcinoma. Acyclovir(ACV) has been already shown to be an effective agent against HSV. However, this compound has side effects and tends to induce resistant virus if used in large amount. A new antibiotics, S632As, glutarimide antibiotics compounds, is a metabolic product from a strain of Antinomyces isolated from soil, and is dealt with in this paper. The purpose of this paper is to study both the agent's inhibition HSV-1 from amplification in vivo and in vitro and its protection infected mice brain tissue, and in an attempt to look for new effective agents. First of all, we evaluate its anti-viral effect in vitro using MTT method and CPE inhibition assay on HSV-1 infected Vero cell. The results show EC50, TC50, TI of S632A3 to the cell by MTT method is 2.5 Mg/ml, 41.5Mg/ml, 16.60 respectively, whereas 3.3Mg/ml, 44.9Mg/ml, 13.61 respectively by CPE inhibition assay. These findings suggest S632A3 can protect susceptible cell in vitro and lessen CPE. On the other hand, on the basis of successfully establishing mice model HSE, we observe post-administration survival rate and mean survival time, examine theviral liter in the brain at intervals after the agent is given and score the extent to which the treated mice brain is injured using pathological HE Staining in order to evaluate its protection the mice brain against HSV-1. The results also show higher doses of S632A3 (28mg/kg) can apparently reduce morbidity of HSV-1 infected mice, prolong the mean survival time, reduce viral titers in brains, lessen lesion of brains and in a word delay the development of related disease. In addition, no statistic significance is found between S632A3(28mg/kg per day) and positive control agent ACV. The paper draws the conclusion that all assays can verify its anti-viral effect in vivo and in vitro and therefore can be prospective agent in the future.