• Title/Summary/Keyword: aAntiviral

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Construction of a Hammerhead Ribozyme that Cleaves Rice Black-Streaked Dwarf Virus RNA (흑조위축병 바이러스 RNA를 절단하는 망치머리형 라이보자임의 제작)

  • Kim, Ju-Kon;Sohn, Seong-Han;Lee, Sug-Soon;Hwang, Young-Soo;Park, Jong-Sug
    • 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.

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Assessing the Effectiveness and Safety of Direct-acting Antiviral Treatment in Korean Patients with Hepatitis C Virus Genotype 1b or 2 at a Tertiary Care Hospital

  • Park, Mi Seon;Yang, Young-Mo;Park, Ki Hyun;Yoon, Hyonok;Kim, Ju Sin;Choi, Eun Joo
    • 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.

Dual-Target Gene Silencing by Using Long, Synthetic siRNA Duplexes without Triggering Antiviral Responses

  • Chang, Chan Il;Kang, Hye Suk;Ban, Changill;Kim, Soyoun;Lee, Dong-ki
    • Molecules and Cells
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    • v.27 no.6
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    • pp.689-695
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    • 2009
  • Chemically synthesized small interfering RNAs (siRNAs) can specifically knock-down expression of target genes via RNA interference (RNAi) pathway. To date, the length of synthetic siRNA duplex has been strictly maintained less than 30 bp, because an early study suggested that double-stranded RNAs (dsRNAs) longer than 30 bp could not trigger specific gene silencing due to the induction of non-specific antiviral interferon responses. Contrary to the current belief, here we show that synthetic dsRNA as long as 38 bp can result in specific target gene silencing without non-specific antiviral responses. Using this longer duplex structure, we have generated dsRNAs, which can simultaneously knock-down expression of two target genes (termed as dual-target siRNAs or dsiRNAs). Our results thus demonstrate the structural flexibility of gene silencing siRNAs, and provide a starting point to construct multifunctional RNA structures. The dsiRNAs could be utilized to develop a novel therapeutic gene silencing strategy against diseases with multiple gene alternations such as viral infection and cancer.

In Vivo Screening Method for the Anti-AIDS Drugs in the BALB/c Mice Inoculated by Anemia Strain of Friend Virus (Friend Anemia Virus에 감염된 BALB/c 생쥐를 이용한 항AIDS약물의 생체내 약효검색)

  • 안형수;염윤기;장영수
    • YAKHAK HOEJI
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    • v.39 no.6
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    • pp.622-630
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    • 1995
  • Inoculation of Friend anemia virus, which was a Kind of retro virus such as HIV, results splenomegaly, anemia, the increase of WBC counts and reverse transcriptase activity in serum. These results were due to the inhibition of the differentiation of erythroid progenitor cell by the FVA at the spleen. Using these as index of antiviral effects, we pursued the establishment of in vivo screening method for the new anti-ADS drugs. Among zidovudine, didanosine and zalcitabine, which were already approved as anti-AIDS drugs, treatment of zidovudine for 18 days in BALB/c mice inoculated with Friend anemia virus resulted the most potent inhibitory effects on the splenomegaly, the increase of WBC counts and reverse transcriptase activity, but did not recovered the anemia due to the tomcity of zidovudhie itself on the bone marrow. The antiviral effects of zidovudine was reduced in case of zidovudine treatment 7 days after Friend anemia virus inoculation. These results suggested that the sooner treatment of zidovudine would be better improved when the virus was inoculated. Human recombinant interferon itself .alpha. did not showed the antiviral activity against Friend anemia virus and did not also affected the antiviral activity of zidovudine. These results suggested that Friend anemia virus would be used as a tool in vivo screening method for the Lobster of reverse transcriptase.

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Synthesis and Antiviral Activity of Novel 2′-Methyl and 4′-Phenyl Branched Carbocyclic Nucleosides (2′-메칠 및 4′-페닐 측쇄를 가진 새로운 카보사이클릭 뉴크레오사이드의 합성 및 항바이러스 약효검색)

  • 양선화;홍준희
    • YAKHAK HOEJI
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    • v.48 no.1
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    • pp.88-92
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    • 2004
  • In this study; a series of 2',4'-doubly branched carbocyclic nucleosides (8,9,10) were synthesized from simple acyclic ketone derivative as starting material. The installation of the 4'-quaternary carbon needed was carried out using a 〔3,3〕-sigmatropic rearrangement. In addition, the introduction of a methyl group in the 2'-position was accomplished by Grig-nard reaction. Bis-vinyl was successfully cyclized using a Grubbs' catalyst II. The natural bases (adenine, cytosine, uracil) were efficiently coupled with the use of a Pd(0) catalyst. Although all the synthesized compounds were assayed against several viruses, only cytosine analogue 9 showed weak antiviral viral activity (EC$_{50}$=45.4 $\mu$M) against CoxB3 virus.s.

Screening of Antiviral Medicinal Plants against Avian Influenza Virus H1N1 for Food Safety

  • Lee, Jang-Hyun;Van, Nguyen Dinh; Ma, Jin-Yeul;Kim, Young-Bong;Kim, Soo-Ki;Paik, Hyun-Dong
    • Food Science of Animal Resources
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    • v.30 no.2
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    • pp.345-350
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    • 2010
  • Various extracts from 30 medicinal plants were evaluated for their antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) and cytotoxicity in MDCK cell culture. The plant material (30 g) was extracted with methanol (300 mL) at room temperature for 24 h, after which the methanolic extracts were filtered, evaporated, and subsequently lyophilized. Evaluation of the potential antiviral activity was conducted by a viral replication inhibition test. Among these medicinal plants, Tussilago farfara, Brassica juncea, Prunus armeniaca, Astragalus membranaceus, Patrinia villosa, and Citrus unshiu showed marked antiviral activity against influenza virus A/H1N1 at concentrations ranging from 0.15625 mg/mL to 1.25 mg/mL, 0.3125 mg/mL to 10 mg/mL, 5 mg/mL to 10 mg/mL, 0.625 mg/mL to 10 mg/mL, 0.625 mg/mL to 10 mg/mL, and 0.3125 mg/mL to 5 mg/mL, respectively. The extracts of Tussilago farfara showed cytotoxicity at concentrations greater than 2.5 mg/mL, whereas the other five main extracts showed no cytotoxicity at concentrations of 10 mg/mL. Taken together, the present results indicated that methanolic extracts of the six main plants might be useful for the treatment of influenza virus H1N1.

Antiviral Potential of the Genus Panax: An updated review on their effects and underlying mechanism of action

  • Yibo Zhang;Xuanlei Zhong;Zhichao Xi;Yang Li;Hongxi Xu
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.183-192
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    • 2023
  • Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

Physico-chemical Characteristics and Antiviral Activity of ASA, an Antibiotic Produced by Actinomycetes B25 (방선균 B25 균주가 생산하는 항생물질 ASA의 물리.화학적 특성 및 항바이러스 활성)

  • 여운형;김영호;박은경;김상석
    • Korean Journal Plant Pathology
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    • v.13 no.1
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    • pp.63-68
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    • 1997
  • In the screening of antiviral materials produced by actinomycetes, an isolate named B25 was fond to produce an antibiotic substance ASA, which showed a strong inhibitory activity against tobacco mosaic virus (TMV) infection. ASA was purified from culture broth of B25 by silica gel column chromatography, preparative TLC, and reversed phase HPLC. Also MS, IR, UV spectrum, and melting point of ASA were determined and analysed. ASA was white powder soluble in dimethyl sulfoxide, chloroform, and ethyl acetate, having absorption peaks at 223 and 328 nm in UV-VIS spectrum, and had a molecular weight of 548. ASA showed strong inhibitory effect on TMV infection when it was applied as a mixture of TMV to the upper surface of leaves of a local lesion host (Nicotiana tabacum c. Xanthi-nc). It also showed antimicrobial effect against yeast and some phytopathogenic fungi.

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Synthesis of (-)-Neplanocin A Analogues as Potential Antiviral Agents

  • Shin, Dae-Hong;Lee, Hyuk-Woo;Park, Sung-Soo;Kim, Joong-Hyup;Jeong, Lak-Shin;Chun, Moon-Woo
    • Archives of Pharmacal Research
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    • v.23 no.4
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    • pp.302-309
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    • 2000
  • Based on (-)-neplanocin A with the 5'-hydroxyl substituted with fluoro, azido, or amino group, the corresponding xylo- and arabino derivatives were synthesized from D-ribose using the Mit-sunobu reaction as a key step. None of the final nucleosides did show either significant antiviral activities or cytotoxicities.

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Stereoselective Synthesis and Antiviral Activity of Novel 4′(α)-Hydroxymethyl and 6′(α)-Methyl Dually Branched Carbocyclic Nucleosides

  • Kim, Jin-Woo;Choi, Bo-Gil;Hong, Joon-Hee
    • Bulletin of the Korean Chemical Society
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    • v.25 no.12
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    • pp.1812-1816
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    • 2004
  • The stereoselective synthesis 4′,6′-dually branched carbocyclic nucleosides was accomplished in this study. The introduction of a methyl group in the 6′$({\alpha})$-position was accomplished by Felkin-Anh controlled alkylation. The construction of the required 4′$({\alpha})$-quaternary carbon was carried out using a [3,3]-sigmatropic rearrangement. Bis-vinyl 6 was successfully cyclized using a Grubbs' catalyst II. The natural bases (adenine, cytosine) were efficiently coupled using a Pd(0) catalyst. When the synthesized compounds were examined for their activity against several viruses such as the HIV-1, HSV-1, HSV-2 and HCMV, the cytosine analogue 13 exhibited good antiviral activity against the HCMV.