Abstract
The first potent inhibitor of HIV proteinase to be licensed by the FDA for anti-AIDS therapy was Ro31-8959 (Invirase™). Approval followed shortly thereafter for ABT-538 (Norvir™) and L-735,524 (Crixivan™). Virus variants have been found to emerge however in patients being treated with these compounds and concerns have been voiced that treatment with one drug might generate resistance not only against that inhibitor but also against the other compounds.1 In patients treated with Ro31-8959, virus variants with decreased sensitivity are selected with the mutations G48V and L90M in the proteinase component of the viral genome,2 whereas with ABT-538 and L-735,524 different resistant mutations have been detected,1,3 e.g. at residues 82 (such as V82F) and 84 (I84V).
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References
Condra, J.H., Schleif, W.A., Blahy, O.M., Gabryelski, L. J., Graham, D. J., Quintero, J. C., Rhodes, A., Rob-bins, H. L., Roth, E., Shivaprakash, M., Titus, D., Yang, T., Teppler, H., Squires, K. E., Deutsch, P.J. & Emini, E.A. (1995). Nature, 374, 569–571.
Jacobsen, H., Yasargil, K., Winslow, D. L., Craig, J. C., Kröhn, A., Duncan, I. A. & Mous, J. (1995). Virology, 206, 527–534.
Molla, A., Korneyeva, M., Gao, Q., Vasavanonda, S., Schipper, P.J., Mo, H.-M., Markowitz, M., Chernyavskiy, T., Niu, P., Lyons, N., Hsu, A., Granneman, G.R., Ho, D. D., Boucher, C. A. B., Leonard, J.M., Norbeck, D. W. & Kempf, D.J. (1996). Nature Med., 2, 760–765.
Erickson, J.W. (1995). Nature Struct. Biol., 2, 523–529.
Wilson, S. I., Phylip, L. H., Mills, J. S., Gulnik, S. V., Erickson, J.W., Dunn, B. M. & Kay, J. (1997). Biochim. Biophys. Acta, in press.
Pettit, S. C., Moody, M. D., Wehbie, R. S., Kaplan, A. H., Nantermet, P.V., Klein, C. A. & Swanstrom, R. (1994). J. Virol., 68, 8017–8027.
Gustchina, A., Kervinen, J., Powell, D.J., Zdanov, A., Kay, J. & Wlodawer, A. (1996). Protein Sci., 5, 1453–1465.
Jacobsen, H., Hanggi, M., Ott, M., Duncan, I. B., Owen, S., Andreoni, M., Vella, S. & Mous, J. (1996). J. Infect. Dis., 173, 1379–1387.
Tisdale, M., Myers, R.E., Maschera, B., Parry, N. R., Oliver, N.M. & Blair, E. D. (1995). Antimicrobial Agents Chemother., 39, 1704–1710.
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Wilson, S.I. et al. (1998). Sensitivity to Inhibition and Catalytic Efficiency of HIV Proteinase Mutants. In: James, M.N.G. (eds) Aspartic Proteinases. Advances in Experimental Medicine and Biology, vol 436. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5373-1_11
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DOI: https://doi.org/10.1007/978-1-4615-5373-1_11
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