Antiviral Activity of Silver Nanoparticles against Hepatitis C Virus Infection
Alaa Mohamed Tamim Mohamed;
Abstract
HCV is a worldwide human pathogen, and most infected patients progress to chronic liver disease. Egypt has the highest HCV prevalence in the world. Today, HCV infection and its complications are among the leading public health challenges in Egypt.
The primary therapy for HCV is treatment with pegylated interferon and ribavirin; however, these agents do not cause a marked decline in the virus titers of all treated patients. Thus, the elucidation of native virus-host interactions is necessary to develop new, more effective therapies. However, the lack of a robust cell culture system to produce infectious virions has hampered research.
The present study aimed to investigate the cytotoxicity and biokinetics of our tested silver nanoparticles in HepG2 cell line and evaluate the antiviral activity of silver nanoparticles in our HCV infected HepG2 cells that supported HCV replication.
Our results could be summarized in the following points:
• The antiproliferative activity of such spherical silver nanoparticles at size of 22 nm and at different concentrations (10 µM, 100 µM and 1000 µM) increased by increasing time of exposure as evaluated by neutral red colorimetric assay and no influence on the cell viability of WISH ( normal cells) by SRB assay.
• The results showed also that IC50 concentration was 111 µM (10.78 mg/L) after 48 h of cell exposure. Additionally, it has revealed that internalization of AgNPs in cellular organelles, cell membrane, cytoplasm, nucleus, mitochondria as shown by TEM.
• The progressive accumulation of cell population in the S phase correlating with decreased number of cells in the G2/M phase after treatment of cells with 100 µM of AgNPs for 24 h. Such results were also confirmed by results of cellular DNA fragmentation which showed lower concentration of cellular DNA extracted from treated cells compared to untreated one.
• The expression of mRNA of p53, BAX, BAK, BCl2 as well as ß actin were observed in untreated and treated HepG2 cells after 24 h of cell exposure to AgNPs at concentration of 100 µM (10.78 mg/L). But, mRNA of caspase3 was not detected in the treated cells at the same time interval.
• The significant inhibition of HCV genotype 4 replication evident by marked decrease in the prominence of amplified HCV viral sequence was observed when HepG2 cells infected with HCV treated with a low silver nanoparticle concentration (50 μM, 0.003mg/ml) for 24 h, which exerted no cytotoxic effect on the cells.
Our future studies aim to investigate the mechanism of antiviral activity of AgNPs against HCV and the impact of exposure time on the potential of AgNPs binding to HCV and preventing virus entry into susceptible cells prior to integration of
The primary therapy for HCV is treatment with pegylated interferon and ribavirin; however, these agents do not cause a marked decline in the virus titers of all treated patients. Thus, the elucidation of native virus-host interactions is necessary to develop new, more effective therapies. However, the lack of a robust cell culture system to produce infectious virions has hampered research.
The present study aimed to investigate the cytotoxicity and biokinetics of our tested silver nanoparticles in HepG2 cell line and evaluate the antiviral activity of silver nanoparticles in our HCV infected HepG2 cells that supported HCV replication.
Our results could be summarized in the following points:
• The antiproliferative activity of such spherical silver nanoparticles at size of 22 nm and at different concentrations (10 µM, 100 µM and 1000 µM) increased by increasing time of exposure as evaluated by neutral red colorimetric assay and no influence on the cell viability of WISH ( normal cells) by SRB assay.
• The results showed also that IC50 concentration was 111 µM (10.78 mg/L) after 48 h of cell exposure. Additionally, it has revealed that internalization of AgNPs in cellular organelles, cell membrane, cytoplasm, nucleus, mitochondria as shown by TEM.
• The progressive accumulation of cell population in the S phase correlating with decreased number of cells in the G2/M phase after treatment of cells with 100 µM of AgNPs for 24 h. Such results were also confirmed by results of cellular DNA fragmentation which showed lower concentration of cellular DNA extracted from treated cells compared to untreated one.
• The expression of mRNA of p53, BAX, BAK, BCl2 as well as ß actin were observed in untreated and treated HepG2 cells after 24 h of cell exposure to AgNPs at concentration of 100 µM (10.78 mg/L). But, mRNA of caspase3 was not detected in the treated cells at the same time interval.
• The significant inhibition of HCV genotype 4 replication evident by marked decrease in the prominence of amplified HCV viral sequence was observed when HepG2 cells infected with HCV treated with a low silver nanoparticle concentration (50 μM, 0.003mg/ml) for 24 h, which exerted no cytotoxic effect on the cells.
Our future studies aim to investigate the mechanism of antiviral activity of AgNPs against HCV and the impact of exposure time on the potential of AgNPs binding to HCV and preventing virus entry into susceptible cells prior to integration of
Other data
| Title | Antiviral Activity of Silver Nanoparticles against Hepatitis C Virus Infection | Other Titles | تأثير جسيمات الفضة النانونية كمضادة للفيروسات ضد الإصابة بفيروس إلتهاب الكبد الوبائى سى | Authors | Alaa Mohamed Tamim Mohamed | Issue Date | 2016 |
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