The entry of entry inhibitors: A fusion of science and medicine

被引:234
|
作者
Moore, JP
Doms, RW
机构
[1] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA
[2] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
关键词
D O I
10.1073/pnas.1932511100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
For HIV-1 to enter a cell, its envelope protein (Env) must sequentially engage CD4 and a chemokine coreceptor, triggering conformational changes in Env that ultimately lead to fusion between the viral and host cell membranes. Each step of the virus entry pathway is a potential target for novel antiviral agents termed entry inhibitors. A growing number of entry inhibitors are under clinical development, with one having already been licensed by the Food and Drug Administration. With the emergence of virus strains that are largely resistant to existing reverse transcriptase and protease inhibitors, the development of entry inhibitors comes at an opportune time. Nonetheless, because all entry inhibitors target in some manner the highly variable Env protein of HIV-1, there are likely to be challenges in their efficient application that are unique to this class of drugs. Env density, receptor expression levels, and differences in affinity and receptor presentation are all factors that could influence the clinical response to this promising class of new antiviral agents.
引用
收藏
页码:10598 / 10602
页数:5
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