• Plant Resources
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• v.4 no.3
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• pp.192-195
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• 2001

Human immunodeficiency virus (HIV), the causative agent of AIDS, still continues to spread rapidly in the world population, especially in Africa and Southeast Asia. At present, two kinds of therapeutic approaches are used for treatment of AIDS. One is to target HIV reverse transcriptase, which is responsible for the viral genome transcription. The other is to inhibit HIV pretense PR, which is essential for the processing of viral proteins. Drug combinations based on these approaches can reduce the blood virus to an undetectable level. However, a small amount of virus may lurk inside the immune cells in a dormant state. Another major obstacle of long-term treatment of the disease is remarkable mutation in HIV. Most of the clinical chemotherapeutic agents have one or more of these problems. High cost and harmful side-effects further reduced the desirability of these drugs. In the course our studies on development of anti-HIV agents from natural products, we investigated various crude drugs for their inhibitory activity against HIV-induced cytopathic effects (CPE) in culture cells, HIV-pretense (PR), HIV-reverse transcriptase (RT) including ribonuclease H (RNase H), and HIV integrase (INT). In the present paper, some inhibitory substances relating to the development of anti-HIV agents are reported.

• BMB Reports
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• v.43 no.12
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• pp.781-788
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• 2010

An often overlooked issue in the field of adenovirus (Ad)-mediated cancer gene therapy is its limited capacity for effective systemic delivery. Although primary tumors can be treated effectively with intralesional injection of conventional Ad vectors, systemic metastasis is difficult to cure. Systemic administration of conventional naked Ads leads to acute accumulation of Ad particles in the liver, induction of neutralizing antibody, short blood circulation half-life, non-specific biodistribution in undesired organs, and low selective accumulation in the target disease site. Versatile strategies involving the modification of viral surfaces with polymers and nanomaterials have been designed for the purpose of maximizing Ad anti-tumor activity and specificity by systemic administration. Integration of viral and non-viral nanomaterials will substantially advance both fields, creating new concepts in gene therapeutics. This review focuses on current advances in the development of smart Ad hybrid nanocomplexes based on various design-based strategies for optimal Ad systemic administration.

• Archives of Pharmacal Research
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• v.15 no.3
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• pp.242-245
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• 1992

Two triterpenes 1 and 2 with antiviral activity against Herpes simplex virus type 1 in vitro were isolated from Prunella vulgaris. Each compound caused a significant reduction in viral cytopathic effect when vero cells were exposed to them for 72 hours after viral challenge. They were identified as betulinic acid (1) and $2\alpha, 3\alpha$-dihydroxyurs-12-en-28-oic acid(2) on the basis of their spectroscopic properties. The antiviral activity of them was estimated as $EC_{50}=30\;\mu$g/ml(1) and $8\;\mu$g/ml(2), respectively by plaque reduction assay.

• Bulletin of the Korean Chemical Society
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• v.26 no.2
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• pp.285-291
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• 2005

The nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) is the viral RNA-dependent RNA polymerase (RdRp), which is the essential catalytic enzyme for the viral replication and is an appealing target for the development of new therapeutic agents against HCV infection. A small amount of serum from a single patient with hepatitis C was used to get the genome of a Korean HCV isolate. Sequence analysis of NS5B 1701 nucleotides showed the genotype of a Korean isolate to be subtype 1b. The soluble recombinant HCV NS5B polymerase lacking the C-terminal 24 amino acids was expressed and purified to homogeneity. With the highly purified NS5B protein, we established in vitro systems for RdRp activity to identify potential polymerase inhibitors. The rhodanine family compounds were found to be potent and specific inhibitors of NS5B from high throughput screening (HTS) assay utilizing the scintillation proximity assay (SPA) system. The binding mode of an inhibitor was analyzed by measuring various kinetic parameters. Lineweaver-Burk plots of the inhibitor suggested it binds not to the active site of NS5B polymerase, but to an allosteric site of the enzyme. The activity of NS5B in in vitro polymerase reactions with homopolymeric RNA requires interaction with multiple substrates that include a template/primer and ribonucleotide triphosphate. Steady-state kinetic parameter, such as Km, was determined for the ribonucleotide triphosphate. One of compounds found interacts directly with the viral polymerase and inhibits RNA synthesis in a manner noncompetitively with respect to UTP. Furthermore, we also investigated the ability of the compound to inhibit NS5B-directed viral RNA replication using the Huh7 cell-based HCV replicon system. The investigation is potentially very useful for the utility of such compounds as anti-hepatitic agents.

• Korean Journal of Veterinary Research
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• v.62 no.3
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• pp.19.1-19.6
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• 2022

Japanese encephalitis virus (JEV) and Akabane virus (AKAV) are mosquito-borne viruses that cause encephalitis and reproductive disorders in horses and cattle, respectively. There is no treatment for JEV or AKAV infections in animals. Therefore, we evaluated the antiviral activity of 18-mer amphipathic peptides in the 1b-4/21-C series on JEV and AKAV using Vero cells in vitro and evaluated their effects on JEV in mice. Of 6 peptides, 1b-4/21-C12 had the lowest IC₅₀ of 0.313 against JEV and its use as an antiviral against JEV and AKAV was examined. The IC₅₀ of 1b-4/21-C12 against JEV and AKAV was 0.78 and 1.14 µM, respectively. Mice treated with 5 or 2 mg/kg of 1b-4/21-C12 had 32% and 16% survival rates, respectively, and the surviving mice treated with 1b-4/21-C12 began to gain weight beginning 8 days post challenge with the virulent Nakayama strain. Moreover, 20 µM 1b-4/21-C peptide had no cytotoxic effects on Vero cells. Our in vitro and in vivo results indicate that 1b-4/21-C12 has antiviral activity against enveloped JEV and AKAV and might be useful as a therapeutic substance.

• Journal of Microbiology
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• v.44 no.2
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• pp.217-225
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• 2006

Kaposi's sarcoma-associated herpesvirus (KSHV) RTA transcription factor is recruited to its responsive elements through interaction with RBP-Jk that is a downstream transcription factor of the Notch signaling pathway that is important in development and cell fate determination. This suggests that KSHV RTA mimics cellular Notch signal transduction to activate viral lytic gene expression. Here, I demonstrated that unlike other B lymphoma cells, KSHV -infected primary effusion lymphoma BCBL1 cells displayed the constitutive activation of ligand-mediated Notch signal transduction, evidenced by the Jagged ligand expression and the complete proteolytic process of Notch receptor I. In order to investigate the effect of Notch signal transduction on KSHV gene expression, human Notch intracellular (hNIC) domain that constitutively activates RBP-Jk transcription factor activity was expressed in BCBL1 cells, TRExBCBL1-hNIC, in a tetracycline inducible manner. Gene expression profiling showed that like RTA, hNIC robustly induced expression of a number of viral genes including KS immune modulatory gene resulting in downregulation of MHC I and CD54 surface expression. Finally, the genetic analysis of KSHV genome demonstrated that the hNIC-mediated expression of KS during viral latency consequently conferred the downregulation of MHC I and CD54 surface expression. These results indicate that cellular. Notch signal transduction provides a novel expression profiling of KSHV immune deregulatory gene that consequently confers the escape of host immune surveillance during viral latency.

• IMMUNE NETWORK
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• v.16 no.4
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• pp.233-241
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• 2016

DCs, like the sensory neurons, express vanilloid receptor 1 (VR1). Here we demonstrate that the VR1 agonists, capsaicin (CP) and resiniferatoxin (RTX), enhance antiviral CTL responses by increasing MHC class I-restricted viral antigen presentation in dendritic cells (DCs). Bone marrow-derived DCs (BM-DCs) were infected with a recombinant vaccinia virus (VV) expressing OVA (VV-OVA), and then treated with CP or RTX. Both CP and RTX increased MHC class I-restricted presentation of virus-encoded endogenous OVA in BM-DCs. Oral administration of CP or RTX significantly increased MHC class I-restricted OVA presentation by splenic and lymph node DCs in VV-OVA-infected mice, as assessed by directly measuring OVA peptide SIINFEKL-K^b complexes on the cell surface and by performing functional assays using OVA-specific CD8 T cells. Accordingly, oral administration of CP or RTX elicited potent OVA-specific CTL activity in VV-OVA-infected mice. The results from this study demonstrate that VR1 agonists enhance anti-viral CTL responses, as well as a neuro-immune connection in anti-viral immune responses.

• Parasites, Hosts and Diseases
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• v.40 no.1
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• pp.45-54
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• 2002

Field trials evaluating selected commercially available mosquito traps variously baited with light, carbon dioxide, and/or octenol were conducted from 18-27 September 2000 in a malarious area near Paekyeon-ri (Tongil-Chon) and Camp Greaves in Paju County, Kyonggi Province, Republic of Korea. The host-seeking activity for common mosquito species, including the primary vector of Japanese encephalitis, Culex tritaeniorhynchus Giles. was determined using hourly aspirator collections from a human and propane lantern-baited Shannon trap doting hours when temperatures exceeded $15^{\circ}C$. The total number of mosquitoes and number of each species captured during the test was compared using a block design. Significant differences were observed for the total number of mosquitoes collected, such that, the Mosquito MagnetTM with octenol > Shannon trap > ABC light trap with light and dry ice > Miniature Black Light trap (manufactured by John W. Hock) $\geq$ New Jersey Trap > ABC light trap with light only. Significant differences in numbers collected among trapes were noted for several species including: Aedes vexans (Meigen), Anopheles lesteri Baisas and Hu. An. sinensis Weidemann, An. sineroides Yamada, An. yatsushiroensis Miyazaki. Culex pipiens pallets Coquillett L., Cx. orientalis Edwards and Cx. tritaeniorhynchus. Host-seeking activity for most common species showed a similar bimodal pattern. Results from these field trap evaluations can significantly enhance current vector and disease surveillance efforts especially for the primary vector of Japanese encephalitis, Cx. tritaeniorhunchus.

• Journal of Life Science
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• v.26 no.1
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• pp.23-33
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• 2016

Pexa-Vec (JX-594) is a specific cancer-targeted oncolytic and immunotherapeutic vaccinia virus. The purpose of this study was to develop methods to maximize the stability of Pexa-Vec. In short-term instability testing, viral activity was rapidly decreased both at 4℃ and at room temperature (RT), but it was completely restored after sonication followed by vortex. Long-term stability testing of Pexa-Vec in the following liquid formulations was performed: (A) 30 mM Tris/pH 7.6, (B) 30 mM Tris/pH 8.6, (C) 30 mM Tris/pH 7.6, 150 mM NaCl, 15% sucrose, (D) 30 mM Tris/pH 7.6, 15% sucrose, and (E) 30 mM Tris/pH 8.6, 15% sucrose. Viral activity decreased less than 2 log10 at 4℃, and RT was observed in 3 days in B, while viral activity was not decreased even after 4–8 weeks at 4℃ and at 1 week in RT in A, suggesting that neutral pH may be essential to maintain virus stability. The addition of 15% sucrose into A (D) significantly increased viral stability at −20℃, 4℃, or RT, and it was also observed at pH 8.6 (E). The addition of 150 mM NaCl into D (C) significantly increased viral stability in addition to the sucrose effect at 4℃ or RT. Accordingly, the viral activity in formulation C was maintained for 1.5 years at 4℃, and for 1-2 weeks in RT. In conclusion, we propose that formulation C can provide the most adequate condition for the proper storage of vaccinia oncolytic virus.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.4
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• pp.489-498
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• 2018

Objective: Foot and mouth disease (FMD) and porcine reproductive and respiratory syndrome (PRRS) are major diseases that interrupt porcine production. Because they are viral diseases, vaccinations are of only limited effectiveness in preventing outbreaks. To establish an alternative multi-resistant strategy against FMD virus (FMDV) and PRRS virus (PRRSV), the present study introduced two genetic modification techniques to porcine cells. Methods: First, cluster of differentiation 163 (CD163), the PRRSV viral receptor, was edited with the clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 technique. The CD163 gene sequences of edited cells and control cells differed. Second, short hairpin RNA (shRNAs) were integrated into the cells. The shRNAs, targeting the 3D gene of FMDV and the open reading frame 7 (ORF7) gene of PRRSV, were transferred into fibroblasts. We also developed an in vitro shRNA verification method with a target gene expression vector. Results: shRNA activity was confirmed in vitro with vectors that expressed the 3D and ORF7 genes in the cells. Cells containing shRNAs showed lower transcript levels than cells with only the expression vectors. The shRNAs were integrated into CD163-edited cells to combine the two techniques, and the viral genes were suppressed in these cells. Conclusion: We established a multi-resistant strategy against viral diseases and an in vitro shRNA verification method.