Molecular Virology

NS5A Amphipatic Helix- Basic Amino Acid PIP2 Pincer (BAAPP) domain

The lab's molecular virology program places a strong emphasis on translating basic research findings into novel antiviral therapies. Current projects include the development of small molecules that target host functions that are essential for the replication of multiple pathogens following the paradigm of "one drug- many viruses".

We have identified a Basic Amino Acid PIP2 Pincer (BAAPP) domain that is present in amphipathic helices in many pathogen proteins, including HCV, Ebola, Enteroviruses 71 and 68, Rhinoviruses among many others. This domain is essential for interaction with phosphatydilinositol 4,5-bisphosphate (PIP2). We are developing inhibitors against proteins in the biosynthesis pathway of PIP2 as novel approaches to target many pathogens that are dependent on this interaction (see Rational Drug Design for more information on small molecule development)

As part of this project, we have developed a new approach for generating mice with humanized livers for in vivo studies of HBV, HDV, HCV and HAV and evaluating novel therapeutic approaches to treat these and other viruses.