scholarly journals Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 705 ◽  
Author(s):  
Pu ◽  
Wang ◽  
Xu ◽  
Lu ◽  
Jiang
Keyword(s):  
Mechanisms Of Action ◽  
Antiretroviral Drugs ◽  
Multiple Drug ◽  
Entry Inhibitors ◽  
Advantages And Disadvantages ◽  
Highly Active ◽  
Multiple Drug Resistant ◽  
Hiv Entry ◽  
Hiv Drugs ◽  
Hiv Entry Inhibitors

Application of highly active antiretroviral drugs (ARDs) effectively reduces morbidity and mortality in HIV-infected individuals. However, the emergence of multiple drug-resistant strains has led to the increased failure of ARDs, thus calling for the development of anti-HIV drugs with targets or mechanisms of action different from those of the current ARDs. The first peptide-based HIV entry inhibitor, enfuvirtide, was approved by the U.S. FDA in 2003 for treatment of HIV/AIDS patients who have failed to respond to the current ARDs, which has stimulated the development of several series of protein- and peptide-based HIV entry inhibitors in preclinical and clinical studies. In this review, we highlighted the properties and mechanisms of action for those promising protein- and peptide-based HIV entry inhibitors targeting the HIV-1 gp120 or gp41 and discussed their advantages and disadvantages, compared with the current ARDs.

scholarly journals HIV entry inhibitors: a new generation of antiretroviral drugs

2005 ◽  
Vol 26 (10) ◽  
pp. 1165-1173 ◽  
Author(s):  
Elias KRAMBOVITIS ◽  
Filippos PORICHIS ◽  
Demetrios A SPANDIDOS
Keyword(s):  
Antiretroviral Drugs ◽  
Entry Inhibitors ◽  
Hiv Entry ◽  
New Generation ◽  
Hiv Entry Inhibitors

scholarly journals HIV entry inhibitors: mechanisms of action and resistance pathways

2006 ◽  
Vol 57 (4) ◽  
pp. 619-627 ◽  
Author(s):  
Verónica Briz ◽  
Eva Poveda ◽  
Vincent Soriano
Keyword(s):  
Mechanisms Of Action ◽  
Entry Inhibitors ◽  
Hiv Entry ◽  
Hiv Entry Inhibitors

The HIV Entry Inhibitors Revisited

2006 ◽  
Vol 13 (8) ◽  
pp. 911-934 ◽  
Author(s):  
J. Leonard ◽  
Kunal Roy
Keyword(s):  
Entry Inhibitors ◽  
Hiv Entry ◽  
Hiv Entry Inhibitors

scholarly journals Development of a Moloney Murine Leukemia Virus-Based Pseudotype Anti-HIV Assay Suitable for Accurate and Rapid Evaluation of HIV Entry Inhibitors

2006 ◽  
Vol 11 (6) ◽  
pp. 652-663 ◽  
Author(s):  
Eva Chan ◽  
Gabrielle Heilek-Snyder ◽  
Nick Cammack ◽  
Surya Sankuratri ◽  
Changhua Ji
Keyword(s):  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Entry Inhibitors ◽  
Hiv Virus ◽  
Ccr5 Antagonists ◽  
Hiv Entry ◽  
Hiv Envelope ◽  
Anti Hiv ◽  
Murine Leukemia ◽  
Hiv Entry Inhibitors

There has been increasing interest in the identification of novel HIV entry inhibitors. For the discovery of these entry inhibitors, robust surrogate anti-HIV assays are highly desired. The authors report a novel anti-HIV assay system using Moloney murine leukemia viruses (MMLVs) pseudotyped with cytoplasmic tail-truncated HIV envelope protein gp140. These pseudotyped MMLV-HIVgp140 viral particles carry luciferase transcripts; therefore, robust luciferase signal can be detected in cells infected by these pseudotypes. Polycationic agent polybrene and spinoculation markedly enhanced the infection efficiency of these pseudotypes. It was demonstrated that the tropism of these pseudotypes is dependent on the pseudotyped HIV envelope proteins. MMLV viruses pseudotyped with gp140 from an R5 HIV virus specifically infect CCR5-expressing cells, and viruses pseudotyped with gp140 from an X4 HIV virus specifically infect CXCR4-expressing cells. Furthermore, CCR5 antagonists inhibited only MMLV-gp140(R5) infections, and CXCR4 antagonists inhibited only MMLV-gp140(X4) infections. A variety of known HIV entry inhibitors were tested in both R5- and X4-dependent pseudotype antiviral assays, and the IC50 values generated were consistent with published results. The pseudotype antiviral assay was also used in the characterization of hundreds of novel CCR5 antagonists. The IC50 values determined in this assay were compared with those determined in HIV antiviral and cell-cell fusion (CCF) assays, and good correlation was found between pseudotype antiviral assay and HIV antiviral assay ( R2 = 0.9) or CCF assay ( R2 = 0.8).

scholarly journals Conformation-dependent recognition of HIV Gp120 by DARPins provides novel possibilities to develop distinct HIV entry inhibitors

Retrovirology ◽  
2012 ◽  
Vol 9 (S2) ◽  
Author(s):  
AM Mann ◽  
N Friedrich ◽  
A Krarup ◽  
P Rusert ◽  
J Weber ◽  
...  
Keyword(s):  
Entry Inhibitors ◽  
Hiv Entry ◽  
Hiv Gp120 ◽  
Hiv Entry Inhibitors

scholarly journals Analysis of HIV Type 1 gp41 and Enfuvirtide Susceptibility among Men in the United States Who Were HIV Infected Prior to Availability of HIV Entry Inhibitors

2009 ◽  
Vol 25 (7) ◽  
pp. 701-705 ◽  
Author(s):  
Sarah E. Hudelson ◽  
Natalia Marlowe ◽  
Wei Huang ◽  
Robert Bruce ◽  
Jessica D. Church ◽  
...  
Keyword(s):  
United States ◽  
The United States ◽  
Entry Inhibitors ◽  
Hiv Entry ◽  
Hiv Type 1 ◽  
Hiv Entry Inhibitors

scholarly journals Novel Compounds Containing Multiple Guanide Groups That Bind the HIV Coreceptor CXCR4

2010 ◽  
Vol 55 (1) ◽  
pp. 255-263 ◽  
Author(s):  
Royce A. Wilkinson ◽  
Seth H. Pincus ◽  
Joyce B. Shepard ◽  
Sarah K. Walton ◽  
Edward P. Bergin ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Entry Inhibitors ◽  
Cxcr4 Receptor ◽  
Arginine Residues ◽  
Hiv Entry ◽  
Low Cytotoxicity ◽  
Potent Antagonist ◽  
Cell Migration And Proliferation ◽  
Hiv 1 ◽  
Hiv Entry Inhibitors

ABSTRACTThe G-protein-coupled receptor CXCR4 acts as a coreceptor for human immunodeficiency virus type 1 (HIV-1) infection, as well as being involved in signaling cell migration and proliferation. Compounds that block CXCR4 interactions have potential uses as HIV entry inhibitors to complement drugs such as maraviroc that block the alternate coreceptor CCR5 or in cancer therapy. The peptide T140, which contains five arginine residues, is the most potent antagonist of CXCR4 developed to date. In a search for nonpeptide CXCR4 ligands that could inhibit HIV entry, three series of compounds were synthesized from 12 linear and branched polyamines with 2, 3, 4, 6, or 8 amino groups, which were substituted to produce the corresponding guanidines, biguanides, or phenylguanides. The resulting compounds were tested for their ability to compete with T140 for binding to the human CXCR4 receptor expressed on mammalian cells. The most effective compounds bound CXCR4 with a 50% inhibitory concentration of 200 nM, and all of the compounds had very low cytotoxicity. Two series of compounds were then tested for their ability to inhibit the infection of TZM-bl cells with X4 and R5 strains of HIV-1. Spermine phenylguanide and spermidine phenylguanide inhibited infection by X4 strains, but not by R5 strains, at low micromolar concentrations. These results support further investigation and development of these compounds as HIV entry inhibitors.

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