期刊
CURRENT OPINION IN HIV AND AIDS
卷 15, 期 5, 页码 300-308出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/COH.0000000000000637
关键词
antibody-dependent cellular cytotoxicity; CD4 mimetics; CD4 mimics; gp120; HIV entry inhibitors; HIV envelope; Phe43 cavity
资金
- CIHR foundation [352417]
- NIH [R01 AI148379, R01 AI150322]
- Canada Research Chair on Retroviral Entry [P01-GM56550/AI150741, RCHS0235]
Purpose of review Close to 2 million individuals globally become infected with HIV-1 each year and just over two-thirds will have access to life-prolonging antivirals. However, the rapid development of drug resistance creates challenges, such that generation of more effective therapies is not only warranted but a necessary endeavour. This review discusses a group of HIV-1 entry inhibitors known as CD4 mimics which exploit the highly conserved relationship between the HIV-1 envelope glycoprotein and the receptor, CD4. Recent findings We review the structure/function guided evolution of these inhibitors, vital mechanistic insights that underpin broad and potent functional antagonism, recent evidence of utility demonstrated in animal and physiologically relevant in-vitro models, and current progress towards effective new-generation inhibitors. Summary The current review highlights the promising potential of CD4 mimetics as multifunctional therapeutics.
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