کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8522954 | 1557785 | 2018 | 40 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Evaluation of antiviral effects of novel NS5A inhibitors in hepatitis C virus cell culture system with full-genome infectious clones
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موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ویروس شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Nonstructural protein 5A (NS5A) inhibitors of hepatitis C virus (HCV) are known to have potent anti-viral effects; however, these inhibitors have limited activities on strains with resistant-associated substitutions or non-genotype 1 strains. To overcome these shortcomings, novel NS5A inhibitors have been developed and approved for clinical application. The aim of this study was to evaluate the anti-viral effect of novel NS5A inhibitors (derivatives of odalasvir) on HCV genotype 2 strains in a cell culture system. Chimeric JFH-1 viruses replaced with NS5A of genotypes 1 and 2 were utilized to assess the genotype-specific potencies of NS5A inhibitors. We also examined full-genome infectious clones of JFH-1, J6cc, and J8cc to confirm the effects of NS5A inhibitors on genotype 2 strains. All chimeric viruses were capable of replication at similar levels in cell culture. We examined the anti-viral effects of derivatives of the novel NS5A inhibitor and compared with the first-generation NS5A inhibitor, daclatasvir (DCV). These compounds inhibited replication of chimeric JFH-1 viruses with NS5A of genotypes 1 and 2Â at low concentrations in comparison with DCV. The EC50 values of J6cc and J8cc to these compounds were more than 100-fold lower than that of DCV. By long-term culture in the presence of these compounds, we obtained highly resistant variants and identified the responsible substitutions. In conclusion, novel NS5A inhibitors displayed improved potency against HCV genotype 2 strains compared with DCV. However, the activity of these compounds was impaired by emerging resistance-associated substitutions.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Antiviral Research - Volume 158, October 2018, Pages 161-170
Journal: Antiviral Research - Volume 158, October 2018, Pages 161-170
نویسندگان
Asako Murayama, Kei Fujiwara, Norie Yamada, Masaaki Shiina, Hussein Hassan Aly, Takahiro Masaki, Masamichi Muramatsu, Takaji Wakita, Takanobu Kato,