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Inhibition of hepatitis C virus 3a genotype entry through Glanthus Nivalis Agglutinin.

Ashfaq UA, Masoud MS, Khaliq S, Nawaz Z, Riazuddin S - Virol. J. (2011)

Bottom Line: The results demonstrated that GNA inhibit the infectivity of HCVpp and HCV infected serum in a dose-dependent manner and resulted in 50% reduction of virus at 1 ± 2 μg concentration.Molecular docking of GNA and HCV glycoproteins (E1 and E2) showed that GNA inhibit HCV entry by binding N-linked glycans.These results demonstrated that targeting the HCV glycans is a new approach to develop antiviral drugs against HCV.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Molecular Medicine, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. usmancemb@gmail.com

ABSTRACT

Background: Hepatitis C Virus (HCV) has two envelop proteins E1 and E2 which is highly glycosylated and play an important role in cell entry. Inhibition of virus at entry step is an important target to find antiviral drugs against HCV. Glanthus Nivalis Agglutinin (GNA) is a mannose binding lectin which has tendency for specific recognition and reversible binding to the sugar moieties of a wide variety of glycoproteins of enveloped viruses.

Results: In the present study, HCV pseudoparticles (HCVpp) for genotype 3a were produced to investigate the ability of GNA to block the HCV entry. The results demonstrated that GNA inhibit the infectivity of HCVpp and HCV infected serum in a dose-dependent manner and resulted in 50% reduction of virus at 1 ± 2 μg concentration. Molecular docking of GNA and HCV glycoproteins (E1 and E2) showed that GNA inhibit HCV entry by binding N-linked glycans.

Conclusion: These results demonstrated that targeting the HCV glycans is a new approach to develop antiviral drugs against HCV.

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Related in: MedlinePlus

Toxicological study of GNA in Huh-7 and CHO cell: Huh-7 cells were plated at the density of 2 × 104in 96 well plates. After 24 h cells were treated with different concentrations of GNA and control consisted of solvent in which GNA dissolved. After 24 h incubation period add MTT solution to all wells and incubated for 3-4 h at 37°C. Viable cells convert MTT to purple formazan crystal. Added DMSO to dissolve the formazan crystals and read absorbance at 570 nm and 620 nm. (a) Toxicological analysis of GNA in Huh-7 cells through MTT cell proliferation assay. (b) Toxicological analysis of GNA in CHO cells through MTT cell proliferation assay.
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Figure 2: Toxicological study of GNA in Huh-7 and CHO cell: Huh-7 cells were plated at the density of 2 × 104in 96 well plates. After 24 h cells were treated with different concentrations of GNA and control consisted of solvent in which GNA dissolved. After 24 h incubation period add MTT solution to all wells and incubated for 3-4 h at 37°C. Viable cells convert MTT to purple formazan crystal. Added DMSO to dissolve the formazan crystals and read absorbance at 570 nm and 620 nm. (a) Toxicological analysis of GNA in Huh-7 cells through MTT cell proliferation assay. (b) Toxicological analysis of GNA in CHO cells through MTT cell proliferation assay.

Mentions: Cytotoxic effects of GNA were analyzed after 24 h incubation of Huh-7 and CHO cells with different concentration of GNA. Figure 2 depicts cytotoxicity analysis of GNA and demonstrates that Huh7 and CHO cell viability is unaffected by concentrations up to 10 μg. However, when exceed from 10 μg, toxic effect in liver and fibroblast cells has been observed. The data verified by microscopic examination of cells and standard trypan blue dye measurement, which demonstrate GNA has no toxic effect at 10 μg concentration.


Inhibition of hepatitis C virus 3a genotype entry through Glanthus Nivalis Agglutinin.

Ashfaq UA, Masoud MS, Khaliq S, Nawaz Z, Riazuddin S - Virol. J. (2011)

Toxicological study of GNA in Huh-7 and CHO cell: Huh-7 cells were plated at the density of 2 × 104in 96 well plates. After 24 h cells were treated with different concentrations of GNA and control consisted of solvent in which GNA dissolved. After 24 h incubation period add MTT solution to all wells and incubated for 3-4 h at 37°C. Viable cells convert MTT to purple formazan crystal. Added DMSO to dissolve the formazan crystals and read absorbance at 570 nm and 620 nm. (a) Toxicological analysis of GNA in Huh-7 cells through MTT cell proliferation assay. (b) Toxicological analysis of GNA in CHO cells through MTT cell proliferation assay.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117843&req=5

Figure 2: Toxicological study of GNA in Huh-7 and CHO cell: Huh-7 cells were plated at the density of 2 × 104in 96 well plates. After 24 h cells were treated with different concentrations of GNA and control consisted of solvent in which GNA dissolved. After 24 h incubation period add MTT solution to all wells and incubated for 3-4 h at 37°C. Viable cells convert MTT to purple formazan crystal. Added DMSO to dissolve the formazan crystals and read absorbance at 570 nm and 620 nm. (a) Toxicological analysis of GNA in Huh-7 cells through MTT cell proliferation assay. (b) Toxicological analysis of GNA in CHO cells through MTT cell proliferation assay.
Mentions: Cytotoxic effects of GNA were analyzed after 24 h incubation of Huh-7 and CHO cells with different concentration of GNA. Figure 2 depicts cytotoxicity analysis of GNA and demonstrates that Huh7 and CHO cell viability is unaffected by concentrations up to 10 μg. However, when exceed from 10 μg, toxic effect in liver and fibroblast cells has been observed. The data verified by microscopic examination of cells and standard trypan blue dye measurement, which demonstrate GNA has no toxic effect at 10 μg concentration.

Bottom Line: The results demonstrated that GNA inhibit the infectivity of HCVpp and HCV infected serum in a dose-dependent manner and resulted in 50% reduction of virus at 1 ± 2 μg concentration.Molecular docking of GNA and HCV glycoproteins (E1 and E2) showed that GNA inhibit HCV entry by binding N-linked glycans.These results demonstrated that targeting the HCV glycans is a new approach to develop antiviral drugs against HCV.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Molecular Medicine, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. usmancemb@gmail.com

ABSTRACT

Background: Hepatitis C Virus (HCV) has two envelop proteins E1 and E2 which is highly glycosylated and play an important role in cell entry. Inhibition of virus at entry step is an important target to find antiviral drugs against HCV. Glanthus Nivalis Agglutinin (GNA) is a mannose binding lectin which has tendency for specific recognition and reversible binding to the sugar moieties of a wide variety of glycoproteins of enveloped viruses.

Results: In the present study, HCV pseudoparticles (HCVpp) for genotype 3a were produced to investigate the ability of GNA to block the HCV entry. The results demonstrated that GNA inhibit the infectivity of HCVpp and HCV infected serum in a dose-dependent manner and resulted in 50% reduction of virus at 1 ± 2 μg concentration. Molecular docking of GNA and HCV glycoproteins (E1 and E2) showed that GNA inhibit HCV entry by binding N-linked glycans.

Conclusion: These results demonstrated that targeting the HCV glycans is a new approach to develop antiviral drugs against HCV.

Show MeSH
Related in: MedlinePlus