Annemarie Laumaea1,2, Amos B Smith3, Joseph Sodroski4,5, Andrés Finzi1,2,6. 1. Centre de Recherche du CHUM. 2. Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada. 3. Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania. 4. Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute. 5. Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA. 6. Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Abstract
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.
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-1envelope 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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