HIV protease drug resistance and its impact on inhibitor design
Ala, P.J.; Rodgers, J.D.; Chang, C.H.
Current Opinion in Drug Discovery and Development 2(4): 265-273
1999
ISSN/ISBN: 1367-6733 PMID: 19649954 Document Number: 506374
The primary cause of resistance to the currently available HIV protease inhibitors is the accumulation of multiple mutations in the viral protease. So far more than 20 substitutions have been observed in the active site, dimer interface, surface loops and flaps of the homodimer. While many mutations reduce the protease's affinity for inhibitors, others appear to enhance its catalytic efficiency. This high degree of genetic flexibility has made the protease an elusive drug target. The design of the next generation of HIV protease inhibitors will be discussed in light of the current structural information.