BENZODIAZEPINE COMPOUNDS WITH ANTI-FLAVIVIRUS ACTIVITY

摘要

The present invention describes a unique antiviral screen system. The assay is based on quantitatively monitoring viral activation of host cell beta-interferon (IFN-beta) gene expression in a HEK293 -derived reporter cell line expressing a firefly luciferase gene under the control of a human IFN-beta promoter. Unlike the traditional high throughput antiviral assays that measure either the reduction of viral components/yields or cytopathic effect, the readout of the reporter assay in the present invention is the virus-induced host cellular innate immune response. Hence, the assay allows for identification of compounds that inhibit virus infection. In addition, because induction of IFN is one of the most common attributes of viruses, the assay is applicable to all the viruses that are able to infect the reporter cell line and induce IFN- beta expression. Compounds that interfere with viral mediated activation of the interferon pathway in a primary screen, can be further screened with virus-specific assay to confirm their antiviral activity.