Development of a dual screening assay for the efficient search for antiviral Hepatitis C entryinhibitors from microorganisms

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The search for more efficient antiviral substances with less side effects is a predominant topic in drug research. Currently, only few viral infectious diseases have satisfactory drug therapies. The pool of natural products continues to be an excellent source for new drug candidates and lead structures. Despite of their great potential natural products are very rarely tested for antiviral activity due to the complexity of cell-based antiviral assays and their lack of high throughput. My research project aims to develop a dual screening approach that allows to screen natural product libraries more efficiently and in a medium throughput for antiviral activity. For this purpose, the biosensor platform Octet® RED96 is used to identify small molecules with high affinities to a target protein in a newly developed protein-based binding assay. For this project I will use the Hepatitis C (HCV) envelope protein E1/E2 to find potential new entryinhibitors. Hits from this binding assay will then be evaluated for entryinhibitory activity in a cell-based assay with single round HCV infectivity assay using HCV-pseudotyped viruses. Active compounds will be fully characterized in terms of structure, activity as well as binding to the viral protein and they will serve immediately as valuable lead structures.This dual screening concept offers a substantially more efficient way to screen for natural products for drug therapy. The combination of the two in vitro assays has the potential to accelerate the drug discovery process and to find antiviral compounds and structural leads that will contribute to the development of new antiviral drugs or serve as molecular probes to study viral infections.