scholarly journals Exposure of HIV-1 to a combination of two carbohydrate-binding agents markedly delays drug resistance development and selects for virus strains with compromised fitness

2013 ◽  
Vol 69 (3) ◽  
pp. 582-593 ◽  
Author(s):  
L. Mathys ◽  
J. Balzarini
Keyword(s):  
Drug Resistance ◽  
Carbohydrate Binding ◽  
Resistance Development ◽  
Binding Agents ◽  
Virus Strains ◽  
Hiv 1

scholarly journals Pradimicin A, a Carbohydrate-Binding Nonpeptidic Lead Compound for Treatment of Infections with Viruses with Highly Glycosylated Envelopes, Such as Human Immunodeficiency Virus

2006 ◽  
Vol 81 (1) ◽  
pp. 362-373 ◽  
Author(s):  
Jan Balzarini ◽  
Kristel Van Laethem ◽  
Dirk Daelemans ◽  
Sigrid Hatse ◽  
Antonella Bugatti ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Human Immunodeficiency Virus ◽  
Prolonged Exposure ◽  
Glycosylation Site ◽  
Carbohydrate Binding ◽  
Genetic Barrier ◽  
Drug Pressure ◽  
Immunodeficiency Virus ◽  
Virus Strains ◽  
Hiv 1

ABSTRACT Pradimicin A (PRM-A), an antifungal nonpeptidic benzonaphtacenequinone antibiotic, is a low-molecular-weight (molecular weight, 838) carbohydrate binding agent (CBA) endowed with a selective inhibitory activity against human immunodeficiency virus (HIV). It invariably inhibits representative virus strains of a variety of HIV-1 clades with X4 and R5 tropisms at nontoxic concentrations. Time-of-addition studies revealed that PRM-A acts as a true virus entry inhibitor. PRM-A specifically interacts with HIV-1 gp120 and efficiently prevents virus transmission in cocultures of HUT-78/HIV-1 and Sup T1 cells. Upon prolonged exposure of HIV-1-infected CEM cell cultures, PRM-A drug pressure selects for mutant HIV-1 strains containing N-glycosylation site deletions in gp120 but not gp41. A relatively long exposure time to PRM-A is required before drug-resistant virus strains emerge. PRM-A has a high genetic barrier, since more than five N-glycosylation site deletions in gp120 are required to afford moderate drug resistance. Such mutated virus strains keep full sensitivity to the other known clinically used anti-HIV drugs. PRM-A represents the first prototype compound of a nonpeptidic CBA lead and, together with peptide-based lectins, belongs to a conceptually novel type of potential therapeutics for which drug pressure results in the selection of glycan deletions in the HIV gp120 envelope.

scholarly journals Inhibition of infection and transmission of HIV-1 and lack of significant impact on the vaginal commensal lactobacilli by carbohydrate-binding agents

2013 ◽  
Vol 68 (9) ◽  
pp. 2026-2037 ◽  
Author(s):  
M. I. Petrova ◽  
L. Mathys ◽  
S. Lebeer ◽  
S. Noppen ◽  
E. J. M. Van Damme ◽  
...  
Keyword(s):  
Carbohydrate Binding ◽  
Binding Agents ◽  
Hiv 1

Capture and transmission of HIV-1 by the C-type lectin L-SIGN (DC-SIGNR) is inhibited by carbohydrate-binding agents and polyanions

2009 ◽  
Vol 83 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Joeri Auwerx ◽  
Katrien O. François ◽  
Els Vanstreels ◽  
Kristel Van Laethem ◽  
Dirk Daelemans ◽  
...  
Keyword(s):  
Carbohydrate Binding ◽  
Binding Agents ◽  
Hiv 1

HIV-1 genetic variation and drug resistance development

2013 ◽  
Vol 11 (11) ◽  
pp. 1159-1178 ◽  
Author(s):  
Sarah Megens ◽  
Kristel Van Laethem
Keyword(s):  
Drug Resistance ◽  
Genetic Variation ◽  
Resistance Development ◽  
Hiv 1

scholarly journals Sensitivity of transmitted and founder human immunodeficiency virus type 1 envelopes to carbohydrate-binding agents griffithsin, cyanovirin-N and Galanthus nivalis agglutinin

2015 ◽  
Vol 96 (12) ◽  
pp. 3660-3666 ◽  
Author(s):  
Bodan Hu ◽  
Tao Du ◽  
Chang Li ◽  
Sukun Luo ◽  
Yalan Liu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Carbohydrate Binding ◽  
Immunodeficiency Virus ◽  
Binding Agents ◽  
Galanthus Nivalis ◽  
Hiv 1 ◽  
Microbicide Candidate

Human immunodeficiency virus type 1 (HIV-1) transmission often results from infection by a single transmitted/founder (T/F) virus. Here, we investigated the sensitivity of T/F HIV-1 envelope glycoproteins (Envs) to microbicide candidate carbohydrate-binding agents (CBAs) griffithsin (GRFT), cyanovirin-N (CV-N) and Galanthus nivalis agglutinin (GNA), showing that T/F Envs demonstrated different sensitivity to CBAs, with IC50 values ranging from 0.006 ± 0.0003 to >10 nM for GRFT, from 0.6 ± 0.2 to 28.9 ± 2.9 nM for CV-N and from 1.3 ± 0.2 to >500 nM for GNA. We further revealed that deglycosylation at position 295 or 448 decreased the sensitivity of T/F Env to GRFT, and at 339 to both CV-N and GNA. Mutation of all the three glcyans rendered a CBA-sensitive T/F Env largely resistant to GRFT, indicating that the sensitivity of T/F Env to GRFT is mainly determined by glycans at 295, 339 and 448. Our study identified specific T/F Env residues associated with CBA sensitivity.

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