Discovery of Novel HIV Entry Inhibitors for the CXCR4 Receptor by Prospective Virtual Screening

2009 ◽  
Vol 49 (4) ◽  
pp. 810-823 ◽  
Author(s):  
Violeta I. Pérez-Nueno ◽  
Sofia Pettersson ◽  
David W. Ritchie ◽  
José I. Borrell ◽  
Jordi Teixidó
Keyword(s):  
Virtual Screening ◽  
Entry Inhibitors ◽  
Cxcr4 Receptor ◽  
Hiv Entry ◽  
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.

Comparison of Ligand-Based and Receptor-Based Virtual Screening of HIV Entry Inhibitors for the CXCR4 and CCR5 Receptors Using 3D Ligand Shape Matching and Ligand−Receptor Docking

2008 ◽  
Vol 48 (3) ◽  
pp. 509-533 ◽  
Author(s):  
Violeta I. Pérez-Nueno ◽  
David W. Ritchie ◽  
Obdulia Rabal ◽  
Rosalia Pascual ◽  
Jose I. Borrell ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Shape Matching ◽  
Entry Inhibitors ◽  
Hiv Entry ◽  
Hiv Entry Inhibitors

Impact of the CXCR4 structure on docking-based virtual screening of HIV entry inhibitors

2012 ◽  
Vol 38 ◽  
pp. 123-136 ◽  
Author(s):  
Jesús M. Planesas ◽  
Violeta I. Pérez-Nueno ◽  
José I. Borrell ◽  
Jordi Teixidó
Keyword(s):  
Virtual Screening ◽  
Entry Inhibitors ◽  
Hiv Entry ◽  
Hiv Entry Inhibitors

scholarly journals Discovery of HIV entry inhibitors via a hybrid CXCR4 and CCR5 receptor pharmacophore‐based virtual screening approach

2020 ◽  
Vol 155 ◽  
pp. 105537 ◽  
Author(s):  
Muhammad Usman Mirza ◽  
Atefeh Saadabadi ◽  
Michiel Vanmeert ◽  
Outi M.H. Salo-Ahen ◽  
Iskandar Abdullah ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Entry Inhibitors ◽  
Screening Approach ◽  
Ccr5 Receptor ◽  
Hiv Entry ◽  
Virtual Screening Approach ◽  
Hiv Entry Inhibitors
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