Our laboratory serves as the Protein Structure Core as a part of the Structural Biology Core Facility for the SERCEB.  The core is a part of the Southeast Regional Center of Excellence for Emerging Infections & Biodefense (SERCEB) , one of the several centers (RCE) funded by National Institute of Health for state-of-the-art research developing therapeutics, vaccines to combat bioterrorism agents.  Currently our group is engaged in structure determination of a number of proteins of pox virus (vaccinia) that are considered to be important drug targets.  Smallpox is one of the most devastating infectious diseases and as a biological weapon it represents a serious threat because of its high fatality rate among unvaccinated persons and the lack of a specific therapy.  Routine vaccination throughout the United States ceased more than a quarter of a century ago.  In a highly susceptible, mobile population, small pox has the potential for spreading rapidly throughout the United States and the world.  Historically smallpox has been used as a biological weapon since the mid eighteenth century.  The stability of the orthopox viruses in aerosol form and the likely small infectious dose would allow the aerosolized virus to disseminate widely.  Smallpox is a DNA virus of the orthopox virus family.  The orthopox viruses are among the largest and most complex of all viruses.  The other members of this genus, monkeypox, vaccinia and cowpox, can also infect man, but only smallpox is readily transmitted from person to person.  No antiviral drugs have yet been proved effective for the treatment of smallpox.

In this program we are using the structural information from a number of potential drug targets of small pox virus for designing and developing novel chemotherapeutic agents.  The targets currently under investigation are deoxyuridine triphosphatase, uracil DNA glycosylase and thymidine kinase.  Availability of high resolution structures of these proteins will aid in design and development of specific inhibitors of this key enzyme.