Natural Product-Based Anti-HIV Drug Discovery and Development Facilitated by the NCI Developmental Therapeutics Program

Yang, Stringner S.; Cragg, Gordon M.; Newman, David J.; Bader, John P.

doi:10.1021/np0003995

Cited by 96 publications

(51 citation statements)

References 85 publications

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“…Pepstatin A is a small pentapeptide produced by several Streptomyces species with a unique hydroxyamino acid (statine) that sterically blocks the active site of HIV-1 protease. 12,13 The outstanding role of microorganisms in the production of antibiotics is notorious. At present, with o1% of the microbial world having been explored, the advances in techniques for microbial cultivation and extraction of nucleic acids from soil and marine habitats are allowing access to a vast untapped reservoir of genetic and metabolic diversity.…”

Section: Introductionmentioning

confidence: 99%

Carbon source regulation of antibiotic production

et al. 2010

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Section: Introductionmentioning

confidence: 99%

Carbon source regulation of antibiotic production

et al. 2010

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“…Medicinal plants are attractive resources for discovering new biologically active natural products to treat many diseases, including infectious diseases (16,17). During the past several decades a great deal of research has been invested natural products from medicinal plants due to the advantages of lower cost, fewer adverse effects, and high chemical diversity of these biologically active molecules.…”

Section: Introductionmentioning

confidence: 99%

Anti-Hepatitis C Virus Activity of a Crude Extract from Longan (<i>Dimocarpus longan</i> Lour.) Leaves

et al. 2016

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SUMMARY:Infection with hepatitis C virus (HCV) results in hepatitis C, a disease characterized by chronic infection, cirrhosis, and hepatocellular carcinoma. Currently, the standard therapy is a combination of pegylated interferon-a plus ribavirin with NS3 protease inhibitors. Addition of NS3 protease inhibitors to the standard therapy improves response rates; however, use of NS3 protease inhibitors is also associated with significant adverse effects and an increase in the overall cost of treatment. Therefore, there is a need to develop safe and inexpensive drugs for the treatment of HCV infections. In this study, we examined the antiviral activity of a crude extract from Dimocarpus longan leaves against HCV (genotype 2a strain JFH1). The D. longan crude extract (DL-CE) exhibited anti-HCV activity with a 50z effective concentration (EC 50 ) of 19.4 mg/ml without cytotoxicity. A time-of-addition study demonstrated that DL-CE has anti-HCV activity at both the entry and post-entry steps and markedly blocks the viral entry step through direct virucidal activity with marginal inhibition of virion assembly. Co-treatment of DL-CE with cyclosporine A, an immunosuppressant or telaprevir, an NS3 protease inhibitor, resulted in additive and synergistic antiviral effects, respectively. Our findings suggest that DL-CE may be useful as an add-on therapy candidate for treating HCV infections.

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“…They include alkaloids, sulphated polysaccharides, polyphenolics, flavonoids, coumarins, phenolics, tannins, triterpenes, lectins, phloroglucinols, lactones, iridoids, depsidones, O-caffeoyl derivatives, lignans, and ribosome inactivating proteins, saponins, xanthones, naphthodianthrones, photosensitisers, phospholipids, quinines and peptides [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Hiv-1 Reverse Transcriptase and Protease Assay of Methanolic Extracts of Adansonia Digitata L.

Sharma

Rangari

2016

Int J Pharm Pharm Sci

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Objective: Anti-HIV activity studies of methanolic extracts of Adansonia digitata L. leaves, root bark and fruit pulp. Methods:Methanolic extracts of A. digitata were tested for HIV enzyme inhibitory activity against HIV-1 reverse transcriptase (RT) and HIV-1 protease (PR). HIV-1 RT assay was performed using non-radioactive HIV-RT colorimetric ELISA kit while the HIV-1 PR assay was performed using a fluorogenic octapeptide substrate, HIV-FRET (fluorescence resonance energy transfer) and a recombinant HIV-1 protease solution (AnaSpec Inc., USA). Results:The percentage inhibition of controls and A. digitata leaves, root bark and fruit pulp extracts were calculated relative to uninhibited HIV-1 RT and PR in 2% DMSO. The results of the HIV-1 RT assay indicated 26.5% inhibition by root bark extract (50 µg/ml) and 12.2% inhibition by leaf extract while the fruit pulp extract (100 µg/ml) has shown only 5.9% inhibition as compared to standard Nevirapine (100 nM) 27.5% inhibition.In the case of HIV-protease assay, leaf extract and fruit pulp extract (50 µg/ml) has shown quite high inhibition (≥ 50%) to the extent of 75% and 74% respectively which is very significant. The root bark extract has shown 35% inhibition. Conclusion:Methanolic extract of the leaves, root bark and fruit pulp of A. digitata has shown low anti-HIV-1 RT but significant PR activity. HIV-1 RT activity of root bark extract and HIV-1 PR activity of fruit pulp extract indicates the potential of the plant as an anti-HIV agent.

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Natural Product-Based Anti-HIV Drug Discovery and Development Facilitated by the NCI Developmental Therapeutics Program

Cited by 96 publications

References 85 publications

Carbon source regulation of antibiotic production

Carbon source regulation of antibiotic production

Anti-Hepatitis C Virus Activity of a Crude Extract from Longan (<i>Dimocarpus longan</i> Lour.) Leaves

Hiv-1 Reverse Transcriptase and Protease Assay of Methanolic Extracts of Adansonia Digitata L.

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