Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro.

Baba, Masanori; Pauwels, Rudi; Balzarini, Jan; Arnout, Jef; Desmyter, Jan; Clercq, Erik De

doi:10.1073/pnas.85.16.6132

Cited by 407 publications

(249 citation statements)

References 25 publications

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“…DS is a biocompatible polymer with an excellent anti‐thrombogenic property 18. Dextran based therapeutics are commonly used in clinics as anti‐thrombotic agents.…”

Section: Discussionmentioning

confidence: 99%

Dextran sulfate as a drug delivery platform for drug‐coated balloons: Preparation, characterization, in vitro drug elution, and smooth muscle cell response

et al. 2015

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Drug‐coated balloons (DCBs) have now emerged as a promising approach to treat peripheral artery disease. However, a significant amount of drug from the balloon surface is lost during balloon tracking and results in delivering only a subtherapeutic dose of drug at the diseased site. Hence, in this study, the use of dextran sulfate (DS) polymer was investigated as a platform to control the drug release from balloons. An antiproliferative drug, paclitaxel (PAT), was incorporated into DS films (PAT‐DS). The characterizations using SEM, FT‐IR, and DSC showed that the films prepared were smooth and homogenous with PAT molecularly dispersed in the bulk of DS matrix in amorphous form. An investigation on the interaction of smooth muscle cells (SMCs) with control‐DS and PAT‐DS films showed that both films inhibited SMC growth, with a superior inhibitory effect observed for PAT‐DS films. PAT‐DS coatings were then produced on balloon catheters. The integrity of coatings was well‐maintained when the balloons were either deflated or inflated. In this study, up to 2.2 µg/mm2 of PAT was loaded on the balloons using the DS platform. Drug elution studies showed that only 10 to 20% of the total PAT loaded was released from the PAT‐DS coated balloons during the typical time period of balloon tracking (1 min) and then ∼80% of the total PAT loaded was released during the typical time period of balloon inflation and treatment (from 1 min to 4 min). Thus, this study demonstrated the use of DS as a platform to control drug delivery from balloons. © 2015 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1416–1430, 2016.

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“…DS is a biocompatible polymer with an excellent anti‐thrombogenic property 18. Dextran based therapeutics are commonly used in clinics as anti‐thrombotic agents.…”

Section: Discussionmentioning

confidence: 99%

Dextran sulfate as a drug delivery platform for drug‐coated balloons: Preparation, characterization, in vitro drug elution, and smooth muscle cell response

et al. 2015

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“…[66,68] In 1988, two independent reports published within months of each other, reported that polyanions such as 1 and 2 reduced the HIV absorption (referred later to as 'entry') on to CD4þ host cells. [69,70] In addition, the study showed that dextran sulfate chain length has no effect on efficacy, however the chain lengths of 2 had a profound effect on HIV-1 inhibition where unfragmented heparin (M w % 15 000 g Á mol À1 ) and long chain fragmented heparin (M w % 11 000 g Á mol À1 ) had the highest efficacy. [70] Although the principle reason for HIV inhibition by sulfated polysaccharides was known, the exact mechanism and the binding site of these polyanionic inhibitors was not known.…”

Section: Polysaccharide Entry Inhibitorsmentioning

confidence: 99%

“…[69,70] In addition, the study showed that dextran sulfate chain length has no effect on efficacy, however the chain lengths of 2 had a profound effect on HIV-1 inhibition where unfragmented heparin (M w % 15 000 g Á mol À1 ) and long chain fragmented heparin (M w % 11 000 g Á mol À1 ) had the highest efficacy. [70] Although the principle reason for HIV inhibition by sulfated polysaccharides was known, the exact mechanism and the binding site of these polyanionic inhibitors was not known. Callahan et al provided indirect evidence showing that 1 had little effect on soluble CD4 (sCD4) binding with gp120 using enzyme linked immunosorbent assay (ELISA).…”

Section: Polysaccharide Entry Inhibitorsmentioning

confidence: 99%

“…[66,69,70] Due to these high in vitro potencies, clinical trials were rapidly set up in the late 1980s to study the efficacy upon systemic administration in HIV-1 infected patients. [129,130] Dextran sulfate (1) was selected as the drug of choice due to low anticoagulant activity compared to heparin (2) and because previous clinical experience in administration of the drug provided a better understanding of the pharmacokinetics and toxicity.…”

Section: Applications and Perspectives Of Anti-hiv Polymer Therapeuticsmentioning

confidence: 99%

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Polymeric Anti‐HIV Therapeutics

Danial

Klok

2014

Macromolecular Bioscience

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The scope of this review is to highlight the application of polymer therapeutics in an effort to curb the transmission and infection of the human immunodeficiency virus (HIV). Following a description of the HIV life cycle, the use of approved antiretroviral drugs that inhibit critical steps in the HIV infection process is highlighted. After that, a comprehensive overview of the structure and inhibitory properties of polymeric anti‐HIV therapeutic agents is presented. This overview will include inhibitors based on polysaccharides, synthetic polymers, dendritic polymers, polymer conjugates as well as polymeric DC‐SIGN antagonists. The review will conclude with a section that discusses the applications of polymers and polymer conjugates as systemic and topical anti‐HIV therapeutics.

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“…Potential retrovirucides or vaginal microbicides include inhibitors of HIV surface glycoprotein and CD4 receptor interaction (3,15,17), virus envelope-disrupting agents (18,25), coreceptor antagonists (11,12), virus-cell fusion inhibitors (4), and viral-uncoating inhibitors (7). Inhibitors of reverse transcription, such as nonnucleoside reverse transcriptase inhibitors (NNRTIs), could also be used as retrovirucides (30).…”

mentioning

confidence: 99%

Development of a New Methodology for Screening of Human Immunodeficiency Virus Type 1 Microbicides Based on Real-Time PCR Quantification

Aguiar

Costa

Pereira

et al. 2007

Antimicrob Agents Chemother

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Potential topical retrovirucides or vaginal microbicides against human immunodeficiency virus type 1 (HIV-1) include nonnucleoside reverse transcriptase inhibitors (NNRTIs). To be successful, such agents have to be highly active against cell-free virions. In the present study, we developed a new real-time PCR-based assay to measure the natural endogenous reverse transcription (NERT) activity directly on intact HIV-1 particles in the presence of reverse transcriptase (RT) inhibitors. We further evaluated the permeability to nevirapine (NVP) and efavirenz (EFV) and their retention within nascent viral particles. We also demonstrated the NVP and EFV inhibitory effects on NERT activity and the impact of resistance mutations measured directly by this new strategy. Furthermore, the results showed a clear correlation between NERT activity and classical infectivity assays. The 50% inhibitory concentrations (IC 50 s) of NVP and EFV were demonstrated to be up to 100-fold higher for cell-free than for cell-associated virions, suggesting that cell-free virions are less permeable to these drugs. Our results suggest that NVP and EFV penetrate both the envelope and the capsid of HIV-1 particles and readily inactivate cell-free virions. However, the characteristics of these NNRTIs, such as lower permeability and lower retention during washing procedures, in cell-free virions reduce their efficacies as microbicides. Here, we demonstrate the usefulness of the NERT real-time PCR as an assay for screening novel antiretroviral compounds with unique mechanisms of action.

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Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro.

Cited by 407 publications

References 25 publications

Dextran sulfate as a drug delivery platform for drug‐coated balloons: Preparation, characterization, in vitro drug elution, and smooth muscle cell response

Dextran sulfate as a drug delivery platform for drug‐coated balloons: Preparation, characterization, in vitro drug elution, and smooth muscle cell response

Polymeric Anti‐HIV Therapeutics

Development of a New Methodology for Screening of Human Immunodeficiency Virus Type 1 Microbicides Based on Real-Time PCR Quantification

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