• Archives of Pharmacal Research
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• 제26권12호
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• pp.1109-1116
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• 2003

A series of 3'- and 4'-branched carbocyclic nucleosides 25, 26, 27, 28, 29 and 30 were synthesized starting from simple acyclic ketone derivatives. The construction of the required quaternary carbon was made using a [3,3]-sigmatropic rearrangement. In addition, the installation of a methyl group in the 3'-position was accomplished using a Horner-Wadsworth-Emmons (HWE) reaction with triethyl 2-phosphonopropionate. Bis-vinyl was successfully cyclized using a Grubbs' catalyst (Ⅱ). Natural bases (adenine, cytosine, uracil) were efficiently coupled with the use of a Pd(0) catalyst.

• Journal of Pharmaceutical Investigation
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• 제20권4호
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• pp.205-208
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• 1990

1-Dodecylazacycloheptan-2-one (Azone) is a new agent that enhances the percutaneous penetration of a number of different chemicals. BVDU and FEAU were evaluated for their potential efficacy in the treatment of cutaneous herpes simplex virus infections by in vitro studies through hairless mouse skin. This study demonstrates the value of penetration enhancing agent (Azone) and the need for a predictable evaluations in the development of topical antiviral agents.

• Archives of Pharmacal Research
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• 제26권9호
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• pp.679-685
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• 2003

A series of novel cyclopropyl nucleosides was synthesized using the highly stereoselective Simmons-Smith reaction starting from 1,2:5,6-di-Ο-isopropylidene-D-mannitol. The structural assignments of these nucleosides were determined by NMR studies and X-ray crystallography. All the synthesized nucleosides were assayed against several viruses.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.233.2-233.2
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• 2002

Apio nucleosides whose 4'-hydroxymethyl group moves to 3'-position exhibit interesting biological activity such as antitumor or antiviral activity. On the other hand. neplanocin A is the representative of the carbocyclic nucleosides and has been recognized as a potent antitumor and antiviral agent. Based on these findings. it was of great interest to design apio neplanocia A which combined the properties of apio nucleosides and neplanocin A. (omitted)

• 한국균학회지
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• 제27권2호통권89호
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• pp.175-179
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• 1999

잔나비걸상 Elfvingia applananta 자실체의 수용성물질 EA의 vesicular stomatitis virus[New Jersey serotype, VSV(NJ)]에 대한 항바이러스효과를 plaque reduction assay에 따라 실험한 결과 EA는 용량의존적으로 plaque 형성을 억제하였으며 $EC_{50}$는 2.10 mg/ml이었다. 단백질성 항바이러스제인 interferon(IFN)과 EA와의 병용시험 결과 f(a)가 0.50에서 0.90인 유효농도범위에서 IFN alpha와 병용시 f(a)의 값이 커짐에 따라 상가작용 내지는 길항작용을 나타내었으며, IFN gamma와의 병용시에는 길항작용을 나타내었다. 따라서 IFN alpha와의 병용시 f(a)가 0.50내지 0.70의 유효농도 범위에서 상가효과가 있다.

• BMB Reports
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• 제53권3호
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• pp.166-171
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• 2020

A chemical library comprising 2,354 drug-like compounds was screened using a transcription and replication-competent viruslike particle (trVLP) system implementing the whole Ebola virus (EBOV) life cycle. Dose-dependent inhibition of Ebola trVLP replication was induced by 15 hit compounds, which primarily target different types of G protein-coupled receptors (GPCRs). Based on the chemical structure, the compounds were divided into three groups, diphenylmethane derivatives, promazine derivatives and chemicals with no conserved skeletons. The third group included sertindole, raloxifene, and ibutamoren showing prominent antiviral effects in cells. They downregulated the expression of viral proteins, including the VP40 matrix protein and the envelope glycoprotein. They also reduced the amount of EBOV-derived tetracistronic minigenome RNA incorporated into progeny trVLPs in the culture supernatant. Particularly, ibutamoren, which is a known agonist of growth hormone secretagogue receptor (GHSR), showed the most promising antiviral activity with a 50% effective concentration of 0.2 μM, a 50% cytotoxic concentration of 42.4 μM, and a selectivity index of 222.8. Here, we suggest a strategy for development of anti-EBOV therapeutics by adopting GHSR agonists as hit compounds.

• Biomolecules & Therapeutics
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• 제26권3호
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• pp.242-254
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• 2018

Defensins are antimicrobial peptides that participate in the innate immunity of hosts. Humans constitutively and/or inducibly express ${\alpha}$- and ${\beta}$-defensins, which are known for their antiviral and antibacterial activities. This review describes the application of human defensins. We discuss the extant experimental results, limited though they are, to consider the potential applicability of human defensins as antiviral agents. Given their antiviral effects, we propose that basic research be conducted on human defensins that focuses on RNA viruses, such as human immunodeficiency virus (HIV), influenza A virus (IAV), respiratory syncytial virus (RSV), and dengue virus (DENV), which are considered serious human pathogens but have posed huge challenges for vaccine development for different reasons. Concerning the prophylactic and therapeutic applications of defensins, we then discuss the applicability of human defensins as antivirals that has been demonstrated in reports using animal models. Finally, we discuss the potential adjuvant-like activity of human defensins and propose an exploration of the 'defensin vaccine' concept to prime the body with a controlled supply of human defensins. In sum, we suggest a conceptual framework to achieve the practical application of human defensins to combat viral infections.

• Journal of Microbiology and Biotechnology
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• 제23권6호
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• pp.771-778
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• 2013

Essential oils are increasingly of interest for use as novel drugs acting as antimicrobial and antiviral agents. In the present study, we report the in vitro antiviral activities of 29 essential oils, extracted from Chinese indigenous aromatic plants, against the tobacco mosaic virus (TMV). Of these essential oils, those oils from ginger, lemon, tea tree, tangerine peel, artemisia, and lemongrass effected a more than 50% inhibition of TMV at 100 ${\mu}g/ml$. In addition, the mode of antiviral action of the active essential oils was also determined. Essential oils isolated from artemisia and lemongrass possessed potent inactivation and curative effects in vivo and had a directly passivating effect on TMV infection in a dose-dependent manner. However, all other active essential oils exhibited a moderate protective effect in vivo. The chemical constitutions of the essential oils from ginger, lemon, tea tree, tangerine peel, artemisia, and lemongrass were identified by gas chromatography and gas chromatography-mass spectrometry. The major components of these essential oils were ${\alpha}$-zingiberene (35.21%), limonene (76.25%), terpinen-4-ol (41.20%), limonene (80.95%), 1,8-cineole (27.45%), and terpinolene (10.67%). The curative effects of 10 individual compounds from the active essential oils on TMV infection were also examined in vivo. The compounds from citronellal, limonene, 1,8-cineole, and ${\alpha}$-zingiberene effected a more than 40% inhibition rate for TMV infection, and the other compounds demonstrated moderate activities at 320 ${\mu}g/ml$ in vivo. There results indicate that the essential oils isolated from artemisia and lemongrass, and the individual compound citronellal, have the potential to be used as an effective alternative for the treatment of tobacco plants infected with TMV under greenhouse conditions.

• Journal of Microbiology and Biotechnology
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• 제26권11호
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• pp.2012-2018
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• 2016

Coxsackievirus B3 (CVB3) is the main cause of acute myocarditis and dilated cardiomyopathy. Plant extracts are considered as useful materials to develop new antiviral drugs. We had previously selected candidate plant extracts, which showed anti-inflammatory effects. We examined the antiviral effects by using a HeLa cell survival assay. Among these extracts, we chose the Amomi Cardamomi (Amomi) extract, which showed strong antiviral effect and preserved cell survival in CVB3 infection. We investigated the mechanisms underlying the ability of Amomi extract to inhibit CVB3 infection and replication. HeLa cells were infected by CVB3 with or without Amomi extract. Erk and Akt activities, and their correlation with virus replication were observed. Live virus titers in cell supernatants and viral positive- and negative-strand RNA amplification were measured. Amomi extract significantly increased HeLa cell survival in different concentrations ($100-10{\mu}g/ml$). CVB3 capsid protein VP1 expression (76%) and viral protease 2A-induced eIF4G1 cleavage (70%) were significantly decreased in Amomi extract ($100{\mu}g/ml$) treated cells. The levels of positive- (20%) and negative-strand (80%) RNA were dramatically decreased compared with the control, as revealed by reverse transcription-PCR. In addition, Amomi extract improved mice survival (51% vs 26%) and dramatically reduced heart inflammation in a CVB3-induced myocarditis mouse model. These results suggested that Amomi extract significantly inhibited Enterovirus replication and myocarditis damage. Amomi may be developed as a therapeutic drug for Enterovirus.

• Archives of Pharmacal Research
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• 제28권4호
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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.