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Opening the HIV envelope: potential of CD4 mimics as multifunctional HIV entry inhibitors

Opening the HIV envelope: potential of CD4 mimics as multifunctional HIV entry inhibitors Downloaded from http://journals.lww.com/co-hivandaids by BhDMf5ePHKbH4TTImqenVJ2toCr/9wZZjwPUWvYES9l2nY+zyylnl33NGMK6MRsx on 10/02/2020 REVIEW URRENT Opening the HIV envelope: potential of CD4 mimics PINION as multifunctional HIV entry inhibitors a,b c d,e Annemarie Laumaea , Amos B. Smith III , Joseph Sodroski , a,b,f and Andre´s Finzi 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. Keywords antibody-dependent cellular cytotoxicity, CD4 mimetics, CD4 mimics, gp120, HIV entry inhibitors, HIV envelope, Phe43 cavity INTRODUCTION or CCR5) (reviewed in [4]). In its unliganded form, the http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Current Opinion in HIV & AIDS Wolters Kluwer Health

Opening the HIV envelope: potential of CD4 mimics as multifunctional HIV entry inhibitors

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Publisher
Wolters Kluwer Health
Copyright
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
ISSN
1746-630X
eISSN
1746-6318
DOI
10.1097/COH.0000000000000637
Publisher site
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Abstract

Downloaded from http://journals.lww.com/co-hivandaids by BhDMf5ePHKbH4TTImqenVJ2toCr/9wZZjwPUWvYES9l2nY+zyylnl33NGMK6MRsx on 10/02/2020 REVIEW URRENT Opening the HIV envelope: potential of CD4 mimics PINION as multifunctional HIV entry inhibitors a,b c d,e Annemarie Laumaea , Amos B. Smith III , Joseph Sodroski , a,b,f and Andre´s Finzi 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. Keywords antibody-dependent cellular cytotoxicity, CD4 mimetics, CD4 mimics, gp120, HIV entry inhibitors, HIV envelope, Phe43 cavity INTRODUCTION or CCR5) (reviewed in [4]). In its unliganded form, the

Journal

Current Opinion in HIV & AIDS – Wolters Kluwer Health

Published: Sep 1, 2020

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