TY - JOUR
T1 - Taking aim at a moving target
T2 - Designing drugs to inhibit drug-resistant HIV-1 reverse transcriptases
AU - Sarafianos, Stefan G.
AU - Das, Kalyan
AU - Hughes, Stephen H.
AU - Arnold, Eddy
N1 - Funding Information:
We thank our colleagues and co-workers, who have made our studies of HIV-1 RT possible, and staff personnel at CHESS, BNLS and APS for support of our X-ray data collection. We are grateful to NIH NIAID and NIGMS (R37 AI 27690 MERIT award and P01 GM 66671) for support of RT structural studies in EA's laboratory. SHH was supported by NIGMS and the NCI.
PY - 2004/12
Y1 - 2004/12
N2 - HIV undergoes rapid genetic variation; this variation is caused primarily by the enormous number of viruses produced daily in an infected individual. Because of this variation, HIV presents a moving target for drug and vaccine development. The variation within individuals has led to the generation of diverse HIV-1 subtypes, which further complicates the development of effective drugs and vaccines. In general, it is more difficult to hit a moving target than a stationary target. Two broad strategies for hitting a moving target (in this case, HIV replication) are to understand the movement and to aim at the portions that move the least. In the case of anti-HIV drug development, the first option can be addressed by understanding the mechanism(s) of drug resistance and developing drugs that effectively inhibit mutant viruses. The second can be addressed by designing drugs that interact with portions of the viral machinery that are evolutionarily conserved, such as enzyme active sites.
AB - HIV undergoes rapid genetic variation; this variation is caused primarily by the enormous number of viruses produced daily in an infected individual. Because of this variation, HIV presents a moving target for drug and vaccine development. The variation within individuals has led to the generation of diverse HIV-1 subtypes, which further complicates the development of effective drugs and vaccines. In general, it is more difficult to hit a moving target than a stationary target. Two broad strategies for hitting a moving target (in this case, HIV replication) are to understand the movement and to aim at the portions that move the least. In the case of anti-HIV drug development, the first option can be addressed by understanding the mechanism(s) of drug resistance and developing drugs that effectively inhibit mutant viruses. The second can be addressed by designing drugs that interact with portions of the viral machinery that are evolutionarily conserved, such as enzyme active sites.
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U2 - 10.1016/j.sbi.2004.10.013
DO - 10.1016/j.sbi.2004.10.013
M3 - Review article
C2 - 15582396
AN - SCOPUS:9944232661
SN - 0959-440X
VL - 14
SP - 716
EP - 730
JO - Current Opinion in Structural Biology
JF - Current Opinion in Structural Biology
IS - 6
ER -