• Journal of Pharmaceutical Investigation
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• v.32 no.4
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• pp.285-290
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• 2002

In order to assay the efficacy of newly synthesized antiviral compounds, in vitro studies of their active intracellular phosphorylated metabolites were established as compared with Zidovudine (ZDV). Antiviral base analogs require intracellular phosphorylation prior to the inhibition of HIV replication. Therefore, antiviral drugs concentrations in plasma have not reflected any direct relationship with activity or toxicity. A method has been developed to measure the concentration of total phosphorylated metabolites inside peripheral blood mononuclear cells using modified commercial radioimmunoassay (RIA). ZDV 5'-monophosphate was synthesized and used as a procedural control for RIA modification. PBMCs were isolated from whole blood and incubated with ZDV for 20 h to allow metabolic phosphorylation. Viable cells were extracted overnight with 60% methanol. After evaporation, the extract was reconstituted in Tris buffer. Samples were split into two fractions, one of which was treated with alkaline phosphatase (AP) to liberate phosphate groups. Concentrations of phosphorylated metabolites were determined by subtracting thε concentration of non-AP-treated fraction from that of the treated fraction. Recovery of phosphorylated ZDV from cell extracts was approximately 90%, and reproducibility was acceptable (coefficients of variation <15% for concentrations${\geq}$0.25 ng/mL). Intracellular concentrations $(0.135{\sim}5.019\;nmole/10^6\;cells)$ followed a nonlinear dose-response relationship over the range $0.015{\sim}2.996mM$ extracellular ZDV, with concentration-dependant saturation.

• YAKHAK HOEJI
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• v.49 no.2
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• pp.151-155
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• 2005

For decades, the demand for new antiviral strategies, especially in hepatitis, has increased markedly due to its devastating pathogenic outcome, In the present study, we examin ed the antiviral effect of the combination of amantadine and biphenyl dimethyl dicarboxylate (DDB) in HepG2 2.2.15, which is transfected with HBV DNA. The study demonstrated that the combination not the single treatment may have an anti-HBV effect through a synergism of antiviral, anti-inflammatory and cytoprotective activities in STAT1 ${\alpha}$, 6-16 gene, and pro-inflammatory components such as nitric oxide and IL-1${\beta}$ expression. In addition, hepatitis B surface and core gene expression were examined as a final end point for the anti-HBV activities, which was also significantly suppressed comparing to normal control (p<0.01).

• Journal of Microbiology and Biotechnology
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• v.31 no.1
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• pp.137-143
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• 2021

Most cervical cancers are associated with high-risk human papillomavirus (HPV) infection. Currently, cervical cancer treatment entails surgical removal of the lesion, but treatment of infection and preventing tissue damage are issues that still remain to be addressed. Herbal medicine and biological studies have focused on developing antiviral drugs from natural sources. In this study, we analyzed the potential antiviral effects of Pinus densiflora Sieb. et Zucc. leaf extracts against HPV. The pine needle extracts from each organic solvent were analyzed for antiviral activity. The methylene chloride fraction (PN-MC) showed the highest activity against HPV pseudovirus (PV). The PN-MC extract was more effective before, rather than after treatment, and therefore represents a prophylactic intervention. Mice were pre-treated with PN-MC via genital application or oral administration, followed by a genital or subcutaneous challenge with HPV PV, respectively. The HPV challenge results showed that mice treated via genital application exhibited complete protection against HPV. In conclusion, PN-MC represents a potential topical virucide for HPV infection.

• Journal of Microbiology and Biotechnology
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• v.30 no.2
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• pp.172-177
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• 2020

Influenza viruses cause respiratory diseases in humans and animals with high morbidity and mortality rates. Conventional anti-influenza drugs are reported to exert side effects and newly emerging viral strains tend to develop resistance to these commonly used agents. Fritillaria thunbergii (FT) is traditionally used as an expectorant for controlling airway inflammatory disorders. Here, we evaluated the therapeutic effects of FT extracts against influenza virus type A (H1N1) infection in vitro, in ovo, and in vivo. In the post-treatment assay, FT extracts showed high CC50 (7,500 ㎍/ml), indicating low toxicity, and exerted moderate antiviral effects compared to oseltamivir (SI 50.6 vs. 222) in vitro. Antiviral activity tests in ovo revealed strong inhibitory effects of both FT extract and oseltamivir against H1N1 replication in embryonated eggs. Notably, at a treatment concentration of 150 mg/kg, only half the group administered oseltamivir survived whereas the FT group showed 100% survival, clearly demonstrating the low toxicity of FT extracts. Consistent with these findings, FT-administered mice showed a higher survival rate with lower body weight reduction relative to the oseltamivir group upon treatment 24 h after viral infection. Our collective results suggest that FT extracts exert antiviral effects against influenza H1N1 virus without inducing toxicity in vitro, in ovo or in vivo, thereby supporting the potential utility of FT extract as a novel candidate therapeutic drug or supplement against influenza.

• The Korean Journal of Pain
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• v.34 no.4
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• pp.509-533
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• 2021

Background: Postherpetic neuralgia (PHN) is a refractory complication of herpes zoster (HZ). To prevent PHN, various strategies have been aggressively adopted. However, the efficacy of these strategies remains controversial. Therefore, we aimed to estimate the relative efficacy of various strategies used in clinical practice for preventing PHN using a network meta-analysis (NMA). Methods: We performed a systematic and comprehensive search to identify all randomized controlled trials. The primary outcome was the incidence of PHN at 3 months after acute HZ. We performed both frequentist and Bayesian NMA and used the surface under the cumulative ranking curve (SUCRA) values to rank the interventions evaluated. Results: In total, 39 studies were included in the systematic review and NMA. According to the SUCRA value, the incidence of PHN was lower in the order of continuous epidural block with local anesthetics and steroids (EPI-LSE), antiviral agents with subcutaneous injection of local anesthetics and steroids (AV + sLS), antiviral agents with intracutaenous injection of local anesthetics and steroids (AV + iLS) at 3 months after acute HZ. EPI-LSE, AV + sLS and AV + iLS were also effective in preventing PHN at 1 month after acute HZ. And paravertebral block combined with antiviral and antiepileptic agents was effective in preventing PHN at 1, 3, and 6 months. Conclusions: The continuous epidural block with local anesthetics and steroid, antiviral agents with intracutaneous or subcutaneous injection of local anesthetics and a steroid, and paravertebral block combined with antiviral and antiepileptic agents are effective in preventing PHN.

• Journal of Microbiology and Biotechnology
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• v.33 no.5
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• pp.600-606
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• 2023

Dengue virus (DENV) is a widespread arbovirus. To efficiently establish infection, DENV evolves multiple strategies to hijack the host innate immune response. Herein, we examined the inhibitory effects of DENV serotype 2 (DENV2) nonstructural proteins on RIG-I-directed antiviral immune response. We found that DENV2 NS2A, NS2B, NS4A, and NS4B significantly inhibited RIG-I-mediated IFN-β promoter activation. The roles of NS2B in RIG-I-directed antiviral immune response are unknown. Our study further showed that NS2B could dose-dependently suppress RIG-I/MAVS-induced activation of IFN-β promoter. Consistently, NS2B significantly decreased RIG-I- and MAVS-induced transcription of IFNB1, ISG15, and ISG56. Mechanistically, NS2B was found to interact with MAVS and IKKε to impair RIG-I-directed antiviral response. Our findings demonstrated a previously uncharacterized function of NS2B in RIG-I-mediated antiviral response, making it a promising drug target for anti-DENV treatments.

• Bulletin of the Korean Chemical Society
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• v.26 no.9
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• pp.1366-1368
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• 2005

The first synthesis of a 4'-branched carbocyclic C-nucleoside 11 was achieved via the key intermediate 6, which was prepared using Knovenagel type condensation from ketone derivative 4.

• Journal of Applied Biological Chemistry
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• v.42 no.4
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• pp.161-165
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• 1999

The antiviral activity of CAP30 from Chenopodium album, a type1 ribosome-inactivating protein (RIP), was examined against 5 different plant viral pathogens, and its activity against Tobacco mosaic virus was compared to those of well known antiviral proteins such as Pokeweed Antiviral protein from leaves and seeds. When the inoculating concentration of Tobacco mosaic virus was varied from 0.4 to $400{\mu}g/ml$, it was observed that CAP30 at the concentration of $1{\mu}g/ml$ suppressed the viral infection of C. amaranthicolor and C. quinoa almost completely up to $40{\mu}g/ml$ Tobacco mosaic virus. Results from the assays for the inhibitions of in vitro translation of rabbit reticulocyte lysate and the suppression of Tobacco mosaic virus infection ($10{\mu}g/ml$) to C. quinoa indicated that CAP30 is a strong inhibitor of protein synthesis and virus infection. The infection of several viruses other than Tobacco mosaic virus to host plants were also inhibited by $5{\mu}g/ml$ CAP30, suggesting that a gene encoding CAP30 can be used to develop transgenic virus-resistant plants.

• Applied Biological Chemistry
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• v.38 no.6
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• pp.522-527
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• 1995

To develop an antiviral agent for the rice black-streaked dwarf virus (RBSDV), a hammerhead type ribozyme, which has a potential target site on the genome segment 3, was designed. Oligonucleotides for the ribozyme and its substrate were synthesized, annealed, and cloned into a plasmid pBluescript II KS(+). Ribozyme and substrate RNAs were then synthesized by in vitro transcription with $T_3$ RNA polymerase, obtaining RNAs in expected size, 193 and 182 nucleotides, respectively. The substrate RNA was efficiently cleaved into two fragments when incubated with the ribozyme at $55^{\circ}C$, while the cleavage was not detected at $37^{\circ}C$. In addition, the segment 3 RNA of RBSDV was also cleaved into two fragments by the same ribozyme at $55^{\circ}C$. Taken together, our results demonstrated that the hammerhead ribozyme has an in vitro endonucleolytic activity and may be used as an antiviral agent in transgenic plants.

• Korean Journal of Clinical Pharmacy
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• v.32 no.3
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• pp.191-203
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• 2022

Background: Direct-acting antivirals are recommended for the treatment of chronic hepatitis C virus in Korea. However, evaluation of direct-acting antiviral regimens in a real-world setting is limited. The aims of this study were to investigate the effectiveness and safety of direct-acting antiviral treatment in Korean patients infected with chronic hepatitis C virus genotype 1b or 2 at a tertiary care hospital. Methods: This was a retrospective study conducted with patient data obtained between August 2015 and August 2019 at Jeonbuk National University Hospital. The primary effectiveness endpoint was sustained virological response 12 weeks post-treatment (SVR12) via intention-to-treat (ITT) and modified intention-to-treat (mITT) analyses. Results: Of the 270 patients, 47.0% were infected with genotype 1b and 53.0% with genotype 2. ITT analysis revealed that SVR12 was achieved in 78.9% of all patients, 77.2% in genotype 1b patients, and 80.4% in genotype 2 patients. Of the 21.1% of all patients who did not achieve SVR12, the majority of treatment failures were non-virologic failures (19.7%). mITT analysis revealed that SVR12 was achieved in 98.2% of all patients, 98.0% in genotype 1b patients, and 98.3% in genotype 2 patients. Almost half of all patients experienced one or more adverse events (43.3%), leading to 2.6% discontinuing scheduled treatment. The most common adverse event was anemia. Conclusions: Direct-acting antiviral-based treatment regimens showed high effectiveness and safety. Non-virological factors, such as premature treatment discontinuation due to adverse events or loss of follow-up, were the major disruptors in achieving SVR12.