Dataset Information

The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications.

ABSTRACT:

Objectives

Lignosulfonic acid (LA), a low-cost lignin-derived polyanionic macromolecule, was extensively studied for its anti-HIV and anti-HSV activity in various cellular assays, its mechanism of viral inhibition and safety profile as potential microbicide.

Results

LA demonstrated potent inhibitory activity of HIV replication against a wide range of R5 and X4 HIV strains and prevented the uptake of HIV by bystander CD4+ T cells from persistently infected T cells in vitro (IC50: 0.07 - 0.34 ?M). LA also inhibited HSV-2 replication in vitro in different cell types (IC50: 0.42 - 1.1 ?M) and in rodents in vivo. Furthermore, LA neutralized the HIV-1 and HSV-2 DC-SIGN-mediated viral transfer to CD4+ T cells (IC50: ~1 ?M). In addition, dual HIV-1/HSV-2 infection in T cells was potently blocked by LA (IC50: 0.71 ?M). No antiviral activity was observed against the non-enveloped viruses Coxsackie type B4 and Reovirus type 1. LA is defined as a HIV entry inhibitor since it interfered with gp120 binding to the cell surface of T cells. Pretreatment of PBMCs with LA neither increased expression levels of cellular activation markers (CD69, CD25 and HLA-DR), nor enhanced HIV-1 replication. Furthermore, we found that LA had non-antagonistic effects with acyclovir, PRO2000 or LabyA1 (combination index (CI): 0.46 - 1.03) in its anti-HSV-2 activity and synergized with tenofovir (CI: 0.59) in its anti-HIV-1 activity. To identify mechanisms of LA resistance, we generated in vitro a mutant HIV-1 NL4.3LAresistant virus, which acquired seven mutations in the HIV-1 envelope glycoproteins: S160N, V170N, Q280H and R389T in gp120 and K77Q, N113D and H132Y in gp41. Additionally, HIV-1 NL4.3LAresistant virus showed cross-resistance with feglymycin, enfuvirtide, PRO2000 and mAb b12, four well-described HIV binding/fusion inhibitors. Importantly, LA did not affect the growth of vaginal Lactobacilli strains.

Conclusion

Overall, these data highlight LA as a potential and unique low-cost microbicide displaying broad anti-HIV and anti-HSV activity.

SUBMITTER: Gordts SC

PROVIDER: S-EPMC4488490 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications.

Gordts Stephanie C SC Férir Geoffrey G D'huys Thomas T Petrova Mariya I MI Lebeer Sarah S Snoeck Robert R Andrei Graciela G Schols Dominique D

PloS one 20150701 7

<h4>Objectives</h4>Lignosulfonic acid (LA), a low-cost lignin-derived polyanionic macromolecule, was extensively studied for its anti-HIV and anti-HSV activity in various cellular assays, its mechanism of viral inhibition and safety profile as potential microbicide.<h4>Results</h4>LA demonstrated potent inhibitory activity of HIV replication against a wide range of R5 and X4 HIV strains and prevented the uptake of HIV by bystander CD4+ T cells from persistently infected T cells in vitro (IC50: 0 ...[more]

PMID: 26132818

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Project description:To avoid the widespread resistance of commercial fungicides, new broad-spectrum botanical fungicides need to be developed. In previous bioactive screening assays, extracts of Artemisia ordosica Krasch. (A. ordosica) had highly antifungal activities, but the responsible phytochemicals were unidentified. In this study, active compounds of A. ordosica extracts were identified using a bioassay-guided method, and antifungal assays were performed in vitro and in vivo. The bioactive compounds were dissolved in petroleum ether, and the best antifungal fraction contained four compounds: trans-dehydromatricaria ester (TDDE), 7, 4-demetylnringenin, capillarin, and stearic acid. Among them, TDDE exhibited the highest antifungal activity against six pathogenic fungi and five bacteria. It exhibited significant fungicidal activity against Thanatephorus cucumeris and Botrytis cinerea with EC50 values of 0.464 μg/mL and 1.4 μg/mL, respectively. The living tissue bioassay results showed that the relative protection effects (RPE) of TDDE on tomato leaves, tomato fruit, and strawberry leaves infected with B. cinerea reached 76.78%, 86.2%, and 80.89%, respectively. In pot experiments, the RPE on tomato and strawberry plants infected with B. cinerea reached 84.11% and 96.37%, respectively. Morphological and physiological examination showed that TDDE had significant inhibitory effects on mycelial growth, including increased top offshoot, contorted hyphal tips, and extravasated cytochylema. Meanwhile, bactericidal activities of TDDE were significantly higher than kanamycin and streptomycin in five bacteria, and the plant tissue experiments further demonstrated that it had an 88.31% RPE on walnut leaves infected with Xanthomonas campestris pv. jugiandis, 72.18% RPE on potato infected with Erwinia carotovora subsp. carotovora, and 82.50% RPE on kiwifruit branches infected with Pseudomonas syringae pv. actinidiae. The active compounds isolated from A. ordosica in this study show great potential value for developing broad-spectrum fungicides, and also provide an important way to identify and isolate new bioactive products from medicinal plants.

Dataset Information

The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications.

Objectives

Results

Conclusion

Publications

The Low-Cost Compound Lignosulfonic Acid (LA) Exhibits Broad-Spectrum Anti-HIV and Anti-HSV Activity and Has Potential for Microbicidal Applications.

Similar Datasets

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