scholarly journals CCR5/CXCR4 Dual Antagonism for the Improvement of HIV Infection Therapy

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 550 ◽  
Author(s):  
Fedora Grande ◽  
Maria Occhiuzzi ◽  
Bruno Rizzuti ◽  
Giuseppina Ioele ◽  
Michele De Luca ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Host Cell ◽  
Membrane Receptor ◽  
Next Generation ◽  
Receptor Antagonists ◽  
Viral Spread ◽  
Early Stages ◽  
Hiv Entry

HIV entry in the host cell requires the interaction with the CD4 membrane receptor, and depends on the activation of one or both co-receptors CCR5 and CXCR4. Former selective co-receptor antagonists, acting at early stages of infection, are able to impair the receptor functions, preventing the viral spread toward AIDS. Due to the capability of HIV to develop resistance by switching from CCR5 to CXCR4, dual co-receptor antagonists could represent the next generation of AIDS prophylaxis drugs. We herein present a survey on relevant results published in the last few years on compounds acting simultaneously on both co-receptors, potentially useful as preventing agents or in combination with classical anti-retroviral drugs based therapy.

Drugs from emasculated hormones: The principle of syntopic antagonism

1989 ◽  
Vol 9 (3) ◽  
pp. 253-272 ◽  
Author(s):  
James Black
Keyword(s):  
Future Research ◽  
Receptor Antagonists ◽  
Personal View ◽  
H2 Receptor Antagonists ◽  
Histamine H2 Receptor ◽  
H2 Receptor ◽  
Early Stages ◽  
Β Receptor

This lecture outlines the early stages in the discovery of adrenaline β-receptor antagonists and of the histamine H2-receptor antagonists. It ends with a brief personal view about future research.

ChemInform Abstract: Nonpeptide Angiotensin II Receptor Antagonists: The Next Generation in Antihypertensive Therapy

ChemInform ◽  
2010 ◽  
Vol 27 (21) ◽  
pp. no-no
Author(s):  
R. R. WEXLER ◽  
W. J. GREENLEE ◽  
J. D. IRVIN ◽  
M. R. GOLDBERG ◽  
K. PRENDERGAST ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Antihypertensive Therapy ◽  
Next Generation ◽  
Angiotensin Ii Receptor ◽  
Angiotensin Ii Receptor Antagonists ◽  
Receptor Antagonists

Dates of HIV infection can be estimated for seroprevalent patients by coalescent analysis of serial next-generation sequencing data

AIDS ◽  
2011 ◽  
Vol 25 (16) ◽  
pp. 2019-2026 ◽  
Author(s):  
Art F.Y. Poon ◽  
Rachel A. McGovern ◽  
Theresa Mo ◽  
David J.H.F. Knapp ◽  
Bluma Brenner ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Hiv Infection ◽  
Next Generation Sequencing Data ◽  
Next Generation ◽  
Sequencing Data ◽  
Coalescent Analysis ◽  
Generation Sequencing

Proteomic analysis of cells in the early stages of herpes simplex virus type-1 infection reveals widespread changes in the host cell proteome

PROTEOMICS ◽  
2009 ◽  
Vol 9 (15) ◽  
pp. 3913-3927 ◽  
Author(s):  
Robin Antrobus ◽  
Kyle Grant ◽  
Bevin Gangadharan ◽  
David Chittenden ◽  
Roger D. Everett ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Host Cell ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Proteomic Analysis ◽  
Early Stages ◽  
Simplex Virus ◽  
Cell Proteome

NK3 receptor antagonists: the next generation of antipsychotics?

2005 ◽  
Vol 4 (12) ◽  
pp. 967-975 ◽  
Author(s):  
Will Spooren ◽  
Claus Riemer ◽  
Herbert Meltzer
Keyword(s):  
Next Generation ◽  
Receptor Antagonists ◽  
Nk3 Receptor

scholarly journals HIV Cell Fusion Assay

2013 ◽  
Vol 19 (1) ◽  
pp. 108-118 ◽  
Author(s):  
Elizabeth B. Smith ◽  
Robert A. Ogert ◽  
David Pechter ◽  
Artjohn Villafania ◽  
Susan J. Abbondanzo ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Fusion ◽  
Chemokine Receptor ◽  
Viral Entry ◽  
Envelope Glycoprotein ◽  
Laser Scanning ◽  
Viral Envelope ◽  
Fusion Event ◽  
Cxcr4 Signaling ◽  
Hiv Entry

The health and disease-related biology of the CXCR4 chemokine receptor presents the challenge of finding a small molecule that can bind CXCR4 and block T-cell tropic human immunodeficiency virus type 1 (HIV-1) cell entry, while preserving the ability of CXCR4 to respond to its native ligand, CXCL12. HIV entry into the host cell involves the interaction of the viral envelope glycoprotein gp120 binding to CD4, followed by a rearrangement in gp120, and subsequent interaction with the chemokine receptor CXCR4 or CCR5. These initial events can be re-created in a cell fusion assay that represents a surrogate system, mimicking the early stages of viral entry via these host cell receptors. In the current study, a T-tropic HIV cell fusion assay was established using U2OS cells expressing the envelope glycoprotein gp160 from the T-tropic HIV NL4-3 and HeLa cells expressing CD4 and CXCR4. Detection of the cell fusion event was based on a Gal4/VP16-activated β-lactamase signal and was measured by automated microscopy or laser scanning plate cytometry. Changes in morphology associated with cell fusion were combined with β-lactamase activity to generate results with robust assay statistics in both 384-well and 1536-well plates. Compounds were subsequently characterized by CXCR4 signaling assays to eliminate functional antagonists and allow the identification of a function-sparing HIV entry inhibitor.

Rilpivirine: a next-generation non-nucleoside analogue for the treatment of HIV infection

2012 ◽  
Vol 13 (7) ◽  
pp. 1007-1014 ◽  
Author(s):  
José Vicente Fernández-Montero ◽  
Eugenia Vispo ◽  
Lourdes Anta ◽  
Carmen de Mendoza ◽  
Vincent Soriano
Keyword(s):  
Hiv Infection ◽  
Nucleoside Analogue ◽  
Next Generation

Interferon-γ Upregulates CCR5 Expression in Cord and Adult Blood Mononuclear Phagocytes

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1137-1144 ◽  
Author(s):  
Deepa Hariharan ◽  
Steven D. Douglas ◽  
Benhur Lee ◽  
Jian-Ping Lai ◽  
Donald E. Campbell ◽  
...  
Keyword(s):  
Cell Surface ◽  
Hiv Infection ◽  
Chemokine Receptors ◽  
Surface Expression ◽  
Interferon Γ ◽  
Mononuclear Phagocytes ◽  
Cell Surface Expression ◽  
Ccr5 Expression ◽  
Hiv Entry ◽  
Ifn Γ

Abstract The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for human immunodeficiency virus (HIV) entry into macrophages. The regulation of their expression influences infectivity by HIV. We report here that interferon-γ (IFN-γ) a cytokine that has bidirectional effects on HIV infection of macrophages, significantly upregulated CCR5 and CCR3 cell surface expression in human mononuclear phagocytes isolated from placental cord blood and adult peripheral blood. Monocytes treated with IFN-γ showed increased chemotaxis to the CCR5 ligands macrophage inflammatory protein-1 (MIP-1) and MIP-1β, confirming the functional relevance of IFN-γ–induced CCR5 expression. However, IFN-γ suppressed HIV entry into macrophages. Interestingly, we demonstrated that IFN-γ inhibited cell surface expression of CD4, the major receptor for HIV. This finding may explain the suppressive effect of IFN-γ on HIV entry into macrophages, despite its enhancing effect on the expression of CCR5 and CCR3 by these cells. In addition, IFN-γ–induced secretion of C-C chemokines (RANTES, MIP-1, and MIP-1β) by mononuclear phagocytes may also suppress HIV entry into macrophages. These data provide further evidence for cytokine-mediated regulation of CCR5 expression and are consistent with a novel paradigm in which cytokines regulate HIV infection and leukocyte migration by reciprocal and opposing effects on the expression of CD4 and chemokine receptors.

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