Ladislau C. Kovari, Ph.D.

Our laboratory performs structure-function studies of viral drug targets using structural, biochemical and computational methods. We use X-ray crystallography and molecular modeling to explore HIV drug resistance, perform structure-based drug design against viruses (HIV-1, hepatitis C virus and SARS virus) and investigate the problem of molecular recognition and protein flexibility. The objective of our research is to understand and overcome the mechanisms of viral resistance in particular as it relates to HIV. To do this we determine the crystal structures of multidrug-resistant HIV-1 protease clinical isolates in order to elucidate the mechanisms of HIV drug resistance and help design the next generation of HIV-1 protease inhibitors.

Vickrey, J.F., Logsdon, B.C., Proteasa, G., Palmer S., Winters, M.A., Merigan, T.C. and Kovari, L.C. HIV-1 protease variants from 100-fold drug resistant clinical isolates: expression, purification and crystallization. Protein Expr. Purif. 28 (1): 165-172, 2003.

Holland-Staley, C.A., Kovari L.C., Golenberg E. and Mayers D. L. Genetic diversity and response to IFN of the NS3 protease gene from clinical strains of the hepatitis C virus Arch. Virol. 147: 1385-1406, 2002.

Winters, M.A., Coolley, K.L., Girard, Y.A., Hamdan, H., Kovari, L.C. and Merigan, T.C. Genotypic, phenotypic, and structural analysis of a deletion in the b3-b4 region of the HIV-1 reverse transcriptase gene that is associated with resistance to nucleoside reverse transcriptase inhibitors. J. Virol. 74:10707- 10713, 2000.

Kovari, L.C., Momany, C., Miyagi, F., Lee, S., Campbell, S., Vuong, B., Vogt, V.M. and Rossmann, M.G. Crystals of Rous sarcoma virus capsid protein show a helical arrangement of protein subunits. Virology 238:79-84, 1997.

Momany, C., Kovari, L.C., Prongay, A., Keller, W., Gitti, R.K., Lee, B.M., Gorbalenya, E., Tong, L., McClure, J., Ehrlich, L.S., Summers, M.D., Carter, C. and Rossmann, M.G. Crystal structure of dimeric HIV-1 capsid protein. Nature Struct. Biol. 3:763-770, 1996.

Kovari, L.C., Momany, C. and Rossmann, M.G. The use of antibody fragments for crystallization and structure determination. Structure 3 (12): 1291-1293, 1995.