Disabling a Killer Virus
The CAMD Protein Crystallography beamline was used to determine the structure of a protein that the Venezuelan Equine Encephalitis (VEE) virus requires for replication. VEE is a mosquito-borne virus found in Central and South America, and southern Texas. Periodic outbreaks infect tens of thousands of people and kill hundreds of thousands of horses, donkeys and mules. The virus was developed into a biological weapon during the Cold War by both the United States and the Soviet Union. There is concern that terrorists could do likewise.
Dr. Andrew Russo, in the lab of Prof. Stanley Watowich, at the University of Texas Medical Branch at Galveston (UTMB), solved the structure of a protein called nsP2 protease. It is an enzyme that divides a large viral protein into smaller segments at specific locations. Only the smaller segments are active for the replication of the virus. Therefore, developing an inhibitor of nsP2 protease would be significant in preventing the virus from replicating and causing encephalitis.
(B) Ribbon diagram of nsP2pro colored from blue (N terminus) to red (C terminus) and including bound water (red spheres).
A knowledge of the structure of nsP2 protease will enable researchers to find potential inhibitors of its function by accessing vast data bases of known compounds that are screened by computers The structure can also be used to design new compounds to test as inhibitors. Prof. Watowich says that potential inhibitors could be available for pre-clinical trials within two years.
The protein was isolated and crystallized at UTMB, and initial data was collected there. The researchers then came to Baton Rouge to use the more powerful x-ray source provided by the CAMD beamline, which is operated by the Gulf Coast Protein Crystallography Consortium (GCPCC). The data generated by CAMD enabled them to see the structure in much greater detail, which is essential for the design of inhibitors.