Viral Proteomics
Summary
The aim of this program was to use viral proteomics for rational viral drug development. The project selected 8 clinically relevant viruses that included HCV, HPV, HIV, HSV, EBV, CMV, vaccinia, and SARS. The group then identified 600 virally-encoded proteins and cloned 80% of their genes into expression vectors. This step was necessary for generating protein crystals and performing protein-protein interaction studies. In total, 50 proteins were purified and 42 protein crystals were generated. Two protein-protein interaction screens revealed one interaction between HIV-rev and Nap1 and another interaction between HSV-ICP27 and HAT1.
Also, the project focused later efforts on 11 viral proteins, one of which was an undisclosed HCV target. Screens to identify inhibitors for this protein uncovered over 200 candidate inhibitors. One undisclosed patent/copyright was reported. The project has received attention in Nature Biotechnology, BioWorld Today, and CBC radio. This project has generated new views on high-throughput crystallization for viral proteins and should lead to new atomic insights that may aid in viral drug design.
Notable Publications
Gao M, Brufatto N, Chen T, Murley LL, Thalakada R, Domagala M, Beattie B, Mamelak D, Athanasopoulos V, Johnson D, McFadden G, Burks C, and Frappier L. 2005. Expression profiling of herpesvirus and vaccinia virus proteins using a high-throughput baculovirus screening system. J. Proteome. Res. 4:2225-35.
