Chemical approaches to study dengue virus

Recently, there has been an explosion of reaction and reagent development at the interface between synthetic chemistry and biology.  These developments have aided the study of numerous biological systems, but little has been explored in chemical virology.  While chemists have modified viral particles to serve as templates for nanostructures, the biochemical toolbox for studying pathogenic viruses is sparse.[1-3]  Viruses can rapidly evolve and new tools are required to meet this ever-changing threat.  While vaccinations have tamed many historically deadly viral diseases, there are still rogue viruses for which no broadly effecacious vaccination strategy is available.  Dengue virus (DENV), the virus that is responsible for dengue fever, hemorrhagic fever, and shock syndrome, is one such pathogen.  DENV has four serotypes that elude cross-immunity.  This fact, coupled with the observation that disease states are heightened upon secondary infections with different serotypes shows that dengue vaccination is not a simple cure.[4]  The WHO estimates that the mosquito-borne pathogen infects over 390 million people each year.  With a rapid increase in severe, potentially fatal, disease forms, DENV poses a significant risk to the 2.5 billion people who live in DENV endemic regions.[5]

We seek to develop tools and strategies to expedite the understanding and treatment of the dengue virus.  These advances will be transferable to other areas of virology and biochemistry.  Along these lines, we are engaged in three core synergistic projects to answer the following questions:

      (1)   Do unnatural metabolites incorporated into DENV serve as reporters for host-pathogen interactions?

      (2)   What are the host-pathogen interactions in DENV that are targetable for diagnosis or treatment?

      (3)   Is there a chemical reaction between two small molecules that reports on the interaction between DENV and  host proteins?

[1] Li, K., et al. Analyst 2010, 135, 21-27.

[2] Strable, E., et al. Bioconjugate Chem. 2008, 19, 866-875.

[3] Banerjee, P. S., et al. J. Am. Chem. Soc. 2010, 132, 13615-13617.

[4] Durbin, A. P.; Whitehead, S. S. in Current Topics in Microbiology and Immunology: Dengue Virus 2010, Rothman, A. L. ,ed. pp. 129-144, London: Springer.

[5] World Health Organization, Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control, 2009.

Bioorthogonal reaction development

Bioorthogonal reactions, those whose components are inert to a complex biological surrounding, have been a driving force behind modern chemical biology.  We are working to develop new reactions and re-appropriate old ones in order to better probe the systems we are interested in.

Cancer treatment

Many of the tools and techniques that we are developing are being made with the idea of having impacts in the area of selective drug delivery.