• Proceedings of the PSK Conference
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• 2003.10b
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• pp.80.2-80.2
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• 2003

The nucleoside analogue, L-FMAUS was synthesized from L-FMAU which has been shown to have significant antiviral acitivity against hepatitis B virus (HBV). The anti-HBV activity and toxicity of the L-FMAUS were examined by a cell culture system using a hepatitis B virus (HBV) producing cell line, HepG2 2.2.15. L-FMAUS was assayed for the inhibition of HBV multiplication by measurement of HBV DNA and surface antigen (HBsAg) levels in the extracellular medium of HepG2 2.2.15 cells after an 8-day treatment. (omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.238.3-239
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• 2003

Among 4'-substituted nucleosides. Nucleocidin. 4'-azido thymidine (ADRT), 4'-fluorinated carbocyclic nucleoside. and 3'-fluoro oxetanosin analogue have demonstrated a variety of biological activities. Since the cyclopentane ring of carbocyclic nucleosides can emulate the furanose moiety. a number of these compounds exhibit interesting biological activity, particularly in the areas of antiviral and anticancer chemotherapy. (omitted)

• Archives of Pharmacal Research
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• v.18 no.5
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• pp.364-365
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• 1995

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.242.1-242.1
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• 2003

The nucleoside analogue, L-FMUS was synthesized from L-FMAU which has been shown to have significant antiviral activity against hepatitis B virus (HBV). It was prepared by two steps. First, 5'hydroxyl of L-FMAU was substituted by thioacetyl group using diisopropylazodicarboxylate(DIAD), Triphenyl phosphine(PPh3) and thioacetic acid in anhydrous THF. (omitted)

• Journal of Microbiology and Biotechnology
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• v.28 no.6
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• pp.849-859
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• 2018

Herpes simplex virus type 2 (HSV-2) infection has been a public health concern worldwide. It is the leading cause of genital herpes and a contributing factor to cervical cancer and human immunodeficiency virus (HIV) infection. No vaccine is available yet for the treatment of HSV-2 infection, and routinely used synthetic nucleoside analogs have led to the emergence of drug resistance. The small molecule $Retro-2^{cycl}$ has been reported to be active against several pathogens by acting on intracellular vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that Retro-2.1, which is an optimized, more potent derivative of $Retro-2^{cycl}$, could inhibit HSV-2 infection, with 50% inhibitory concentrations of $5.58{\mu}M$ and $6.35{\mu}M$ in cytopathic effect inhibition and plaque reduction assays, respectively. The cytotoxicity of Retro-2.1 was relatively low, with a 50% cytotoxicity concentration of $116.5{\mu}M$. We also preliminarily identified that Retro-2.1 exerted the antiviral effect against HSV-2 by a dual mechanism of action on virus entry and late stages of infection. Therefore, our study for the first time demonstrated Retro-2.1 as an effective antiviral agent against HSV-2 in vitro with targets distinct from those of nucleoside analogs.

• Archives of Pharmacal Research
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• v.28 no.4
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• pp.451-457
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• 2005

Experimental studies have demonstrated that the triple combination of amantadine (A)/ ursodeoxycholic acid (UDCA, U)/ biphenyl dimethyl dicarboxylate (DDB, D) might have a preferential antiviral effect compared with that observed in interferon-induced antiviral signal pathways, such as those of $STAT1\alpha$ and the 6-16 genes. To confirm the results, this study examined whether th signal transduction for the antiviral activity in HepG2 2.2.15 was induced dependently or independently of interferon. To accomplish this, the correlation between the $STAT1\alpha$ and 6-16 genes, and nitric oxide, for the mediation of the antiviral activity was assessed. The increase in nitric oxide in the UDCA groups suggests that the inhibition of viral gene replication was enhanced by the amantadine combinations (AU and AUD), and might be more effective if incubated for longer periods. It was found that $STAT1\alpha$ was activated by the amantadine combination, although to a lesser extent than that of $interferon-\alpha$, and the primary endpoints examined for the inhibition of gene expression (HBsAg and HBcAg) were remarkably well regulated. This suggests that the amantadine triple, or at least the double, combination had better clinical benefits than those of $IFN-\alpha$ and the nucleoside analogue single treatment. This demonstrates that the amantadine combination might be a substitute for the existing HBV therapy if the results of in vivo and in vitro studies concur.

• Biomolecules & Therapeutics
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• v.7 no.2
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• pp.158-163
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• 1999

In order to find less toxic antiherpetic agents, antiviral activities of quercitrin against two strains of pathogenic viruses such as herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) were determined in Vero cells using plaque reduction assay in vitro. Quercitrin showed a concentration-dependent decrease in plaque formation of HSV-1 and HSV-2. It also exhibited more potent antiherpetic activity on HSV-1 with 50% effective concentration (EC$_{50}$) of 20.4 $\mu$g/ml than on HSV-2 with EC$_{50}$ of 30.4 $\mu$g/ml. The combined antiherpetic effects of quercitrin with nucleoside antiherpetic agents, acyclovir and vidarabine, were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combinations of quercitrin with acyclovir and vidarabine on HSV-1 showed more potent synergism with CI values of 0.27-0.81 for 50%, 70%, 90% effective levels than those on HSV-2 with CI values of 1.03~2.20..20.

• Molecules and Cells
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• v.21 no.3
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• pp.330-336
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• 2006

Since its identification in 1989, hepatitis C virus has been the subject of extensive research. The biology of the virus and the development of antiviral drugs are closely related. The RNA polymerase activity of nonstructural protein 5B was first demonstrated in 1996. NS5B is believed to localize to the perinuclear region, forming a replicase complex with other viral proteins. It has a typical polymerase structure with thumb, palm, and finger domains encircling the active site. A de novo replication initiation mechanism has been suggested. To date, many small molecule inhibitors are known including nucleoside analogues, non-nucleoside analogues, and pyrophosphate mimics. NS5B interacts with other viral proteins such as core, NS3, 4A, 4B, and 5A. The helicase activity of NS3 seems necessary for RNA strand unwinding during replication, with other nonstructural proteins performing modulatory roles. Cellular proteins interacting with NS5B include VAMP-associated proteins, heIF4AII, hPLIC1, nucleolin, PRK2, ${\alpha}$-actinin, and p68 helicase. The interactions of NS5B with these proteins might play roles in cellular trafficking, signal transduction, and RNA polymerization, as well as the regulation of replication/translation processes.

• The Journal of Korean Society of Virology
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• v.27 no.1
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• pp.69-75
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• 1997

To evaluate in vitro anti-HIV efficacies of nucleoside derivatives, MT-4 cell line was infected with HIV-1 and HIV-2 respectively and treated with various compounds and the formerly approved drugs such as AZT, d4T, ddC and ddI. CPE method was used to evaluate their antiviral activity. Most dideoxynucleosides, AZT, d4T, ddC and ddI, showed anti-HIV activities against both viruses but no other compounds including anti-herpesvirus drugs did any. Further experiments were carried out to study their inhibitory mechanism of viral adsorption. The results showed no inhibition of syncytium formation due to an interaction between the gp120 expressed in HIV -infected cell surface and CD4 receptor on the uninfected cell surface in the presence of AZT. AZT showed no activity up to $100\;{\mu}g/ml$. Inhibition of reverse transcriptase (RT) in the presence of AZT-triphosphate was tested by using RT expressed in E. coli and purified and its $IC_{50}$ was 4.5 nM.

• Natural Product Sciences
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• v.5 no.2
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• pp.107-111
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• 1999

To investigate less toxic antiviral agents from Basidiomycetes, EA, the water soluble substance, was isolated from the carpophores of Elfvingia applanata (pers.) Karst. Anti-varicella zoster virus (Oka strain; anti-VZV/Oka) activity of EA was examined in MRC-5 cells by plaque reduction assay in vitro. And the combined antiviral effects of EA with nucleoside anti-VZV agents, acyclovir and vidarabine, were examined on the multiplication of VZV/Oka. EA exhibited a concentration-dependent reduction in the plaque formation of VZV/Oka with a 50% effective concentration $(EC_{50})$ of $464.14\;{\mu}g/ml$. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combination of EA with acyclovir showed more potent synergism with CI values of $0.18{\sim}0.62$ for $50{\sim}90%$ effective levels than that of EA with vidarabine with CI values of $0.67{\sim}1.04$.