TXU (Anti-CD7)-Pokeweed Antiviral Protein as a Potent Inhibitor of Human Immunodeficiency Virus

Uçkun, Fatih M.; Chelstrom, Lisa M.; Tuel‐Ahlgren, Lisa; Dıbırdık, İlker; Irvin, James D.; Langlie, Mridula-Chandan; Myers, Dorothea E.

doi:10.1128/aac.42.2.383

Cited by 73 publications

(27 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The first report of a clinical pharmacokinetic study of TXU (anti-CD7)-PAP immunoconjugate in HIV-infected patients was reported with superior in vitro anti-HIV-1 activity of PAP compared with the activity of zidovudine (Uckun et al 1998). These observations may provide the basis for further investigation of PAP as a potential biotherapeutic agent for HIV patients.…”

Section: Future Prospectsmentioning

confidence: 91%

Novel antiviral agents: a medicinal plant perspective

2003

View full text Add to dashboard Cite

SUMMARYSeveral hundred plant and herb species that have potential as novel antiviral agents have been studied, with surprisingly little overlap. A wide variety of active phytochemicals, including the flavonoids, terpenoids, lignans, sulphides, polyphenolics, coumarins, saponins, furyl compounds, alkaloids, polyines, thiophenes, proteins and peptides have been identified. Some volatile essential oils of commonly used culinary herbs, spices and herbal teas have also exhibited a high level of antiviral activity. However, given the few classes of compounds investigated, most of the pharmacopoeia of compounds in medicinal plants with antiviral activity is still not known. Several of these phytochemicals have complementary and overlapping mechanisms of action, including antiviral effects by either inhibiting the formation of viral DNA or RNA or inhibiting the activity of viral reproduction. Assay methods to determine antiviral activity include multiple-arm trials, randomized crossover studies, and more compromised designs such as nonrandomized crossovers and preand post-treatment analyses. Methods are needed to link antiviral efficacy/potency-and laboratory-based research. Nevertheless, the relative success achieved recently using medicinal plant/herb extracts of various species that are capable of acting therapeutically in various viral infections has raised optimism about the future of phyto-antiviral agents. As this review illustrates, there are innumerable potentially useful medicinal plants and herbs waiting to be evaluated and exploited for therapeutic applications against genetically and functionally diverse viruses families such as Retroviridae, Hepadnaviridae and Herpesviridae.

show abstract

Section: Future Prospectsmentioning

confidence: 91%

Novel antiviral agents: a medicinal plant perspective

2003

View full text Add to dashboard Cite

show abstract

“…Predictable activities. Compounds 3a to 3d were tested for RT inhibitory activity in cell-free assays using purified HIV RT (listed as IC 50 [rRT] in Table 2), as well as by in vitro assays of anti-HIV activity in human T-cell leukemia virus IIIB (HTLV-IIIB)-infected PBMNC (22,47,49) Table 2). Compound 3a, which showed the lowest activity and the worst interaction scores, inhibited rRT in two independent experiments with IC 50 s of 38.…”

Section: Resultsmentioning

confidence: 99%

“…Normal human PBMNC from HIVnegative donors were cultured for 72 h in RPMI 1640 medium supplemented with 20% (vol/vol) heat-inactivated fetal bovine serum, 3% interleukin-2, 2 mM L-glutamine, 25 mM HEPES, 2-g/liter NaHCO 3 , 50-g/ml gentamicin, and 4g/ml phytohemagglutinin prior to exposure to HIV-1 at a multiplicity of infection of 0.1 during a 1-h adsorption period at 37°C in a humidified 5% CO 2 atmosphere. Subsequently, cells were cultured in 96-well microtiter plates (100 l/ well; 2 ϫ 10 6 cells/ml, triplicate wells) in the presence of various inhibitor concentrations, and aliquots of culture supernatants were removed from the wells on day 7 after infection for antigen p24 enzyme immunoassays (EIA), as previously described (22,47,49). The applied p24 EIA was the unmodified kinetic assay commercially available from Coulter Corporation/Immunotech, Inc. (Westbrooke, Maine), which utilizes a murine monoclonal antibody to HIV core protein used to coat microwell strips to which the antigen present in the test culture supernatant samples binds.…”

Section: Construction Of the Nni Composite Binding Pocketmentioning

confidence: 99%

Structure-Based Design of Novel Dihydroalkoxybenzyloxopyrimidine Derivatives as Potent Nonnucleoside Inhibitors of the Human Immunodeficiency Virus Reverse Transcriptase

Sudbeck

Chen

Vig

et al. 1998

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Two highly potent dihydroalkoxybenzyloxopyrimidine (DABO) derivatives targeting the nonnucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been designed based on the structure of the NNI binding pocket and tested for anti-HIV activity. Our lead DABO derivative, 5-isopropyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-one, elicited potent inhibitory activity against purified recombinant HIV RT and abrogated HIV replication in peripheral blood mononuclear cells at nanomolar concentrations (50% inhibitory concentration, <1 nM) but showed no detectable cytotoxicity at concentrations as high as 100 μM.

show abstract

“…The IC 50 values were determined using the Statview statistics program (SAS Institute, San Francisco, CA, USA). In parallel, the effects of various treatments on cell viability were also examined as previously described [36]. In brief, nonin-fected PBMC were treated with each compound for 5 days under identical experimental conditions.…”

Section: Antiviral Susceptibility Assaysmentioning

confidence: 99%

In vitro Activity of Stampidine against Primary Clinical Human Immunodeficiency Virus Isolates

Uckun

Pendergrass

Qazi

et al. 2011

Arzneimittelforschung

View full text Add to dashboard Cite

The in vitro activity profile of stampidine (CAS 217178-62-6, STAMP) was examined against clinical isolates of HIV-1. In a side-by-side comparison against 10 zidovudine-sensitive clinical HIV-1 isolates, STAMP was 100-fold more potent than stavudine (CAS 3056-17-5) and twice as effective as zidovudine (CAS 30516-87-1). STAMP was also active against phenotypically and/or genotypically NRTI (nucleoside analog inhibitors of reverse transcriptase) -resistant HIV and inhibited the replication of 20 zidovudine-resistant clinical HIV-1 isolates with low nanomolar to subnanomolar IC50 values. Similarly, STAMP inhibited the replication of 9 genotypically NNRTI (non-nucleoside analog inhibitors of reverse transcriptase)-resistant clinical HIV-1 isolates (n = 9) with an average IC50 value of 11.2 +/- 6.5 nmol/L. The remarkable potency of STAMP against clinical HIV-1 isolates with NRTI- or NNRTI-resistance warrants the further development of this promising new antiviral agent.

show abstract

TXU (Anti-CD7)-Pokeweed Antiviral Protein as a Potent Inhibitor of Human Immunodeficiency Virus

Cited by 73 publications

References 21 publications

Novel antiviral agents: a medicinal plant perspective

Novel antiviral agents: a medicinal plant perspective

Structure-Based Design of Novel Dihydroalkoxybenzyloxopyrimidine Derivatives as Potent Nonnucleoside Inhibitors of the Human Immunodeficiency Virus Reverse Transcriptase

In vitro Activity of Stampidine against Primary Clinical Human Immunodeficiency Virus Isolates

Contact Info

Product

Resources

About