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


Journal

Current opinion in HIV and AIDS
ISSN: 1746-6318
Titre abrégé: Curr Opin HIV AIDS
Pays: United States
ID NLM: 101264945

Informations de publication

Date de publication:
09 2020
Historique:
entrez: 10 8 2020
pubmed: 10 8 2020
medline: 19 8 2021
Statut: ppublish

Résumé

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. 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. The current review highlights the promising potential of CD4 mimetics as multifunctional therapeutics.

Identifiants

pubmed: 32769632
doi: 10.1097/COH.0000000000000637
pii: 01222929-202009000-00006
pmc: PMC7737667
mid: NIHMS1651346
doi:

Substances chimiques

CD4 Antigens 0
HIV Envelope Protein gp120 0
HIV Fusion Inhibitors 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

300-308

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI148379
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI150471
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150322
Pays : United States
Organisme : NIGMS NIH HHS
ID : P01 GM056550
Pays : United States
Organisme : CIHR
ID : 352417
Pays : Canada
Organisme : NIAID NIH HHS
ID : U01 AI150741
Pays : United States

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Auteurs

Annemarie Laumaea (A)

Centre de Recherche du CHUM.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.

Amos B Smith (AB)

Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania.

Joseph Sodroski (J)

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute.
Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA.

Andrés Finzi (A)

Centre de Recherche du CHUM.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.

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Classifications MeSH