• 대한한방내과학회지
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• 제21권2호
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• pp.291-297
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• 2000

Objective : In order to find antiviral compounds against Herpes simplex virus type I(HSV-1) and II(HSV-2) from herb medicines, a convenient virus-induced cytopathic effect(CPE) inhibition assay was introduced. Methods : Fourteen purchased herbal medicines, and their toxicity of infected cell and anti-viral activities were evaluated. Among them, the major part of herbal medicines showed cell stability compared with the contrast. Results : Cytotoxic concentration (CC) of the $H_2O$ extracts of Hyongbangpaedoksan against HSV-1 and HSV-2 was 181.12. This is high level cytotoxic concentration compared with the contrast. Therefore, we assumed that the high level cytotoxic concentration of herbal medicine play a major role in improvement of antiviral activity at the first infective cell. But antiviral effect was unable to figure out for selective index(Sl)=CC50/EC50. The other herbal medicines were unable to showed potent anti-HSV activity. Conclusions : The antiviral activation using herbs in this thesis have unlimited objects, to select research object will help to show the direction of antiviral drug development that have less side effect and more excellent efficiency.

• 생약학회지
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• 제30권2호
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• pp.151-157
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• 1999

In order to find less toxic antiherpetic agents, the effect of natural quercetin on the plaque formation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was studied in vitro in cell culture monolayers employing the technique of viral plaque reduction assay. Quercetin caused a concentration-dependent reduction in the plaque formation of herpesviruses. It also exhibited more potent antiherpetic activity on HSV-1 with effective concentration $(EC_{50})$ of $18.7\;{\mu}g/ml$ than on HSV-2 with $EC_{50}$ of $24.5\;{\mu}g/ml$. The combined antiherpetic effects of quercetin 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 quercetin with acyclovir on HSV-1 and HSV-2 showed more potent synergism with CI values of $0.19{\sim}0.89$ for 50%, 70%, 90% effective levels than those with vidarabine with CI values of $0.43{\sim}1.46$.

• 대한핵의학회지
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• 제36권2호
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• pp.102-109
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• 2002

목적: 유전자 치료에서, 종양세포에 herpes simplex virus thymidine kinase 유전자를 발현시키고 이에 민감한 prodrug을 전신투여하여 발현된 종양세포에 특이적으로 집적되는 방법은 매우 효율적인 방법이다. 대표적인 prodrug인, IVDU, IVFRU는 herpes simplex virus type 1의 비침습적 영상화 방법에 응용되는 방사옥소 표지가능 화합물이다. 재료 및 방법: Trans-l-trimethylsilyl-2-tri-n-butylstannylethylene과 uridine 변형체상의 iodo-uracil을 Pd촉매하에서 반응시켜 표지전구체인 5-trimethylvinyl-deoxy-uridine과 5-trimethylsilylvinyl-deoxy-fluororibofuranosyl uracil을 합성하였다. 이것을 column chromatography의 방법으로 분리 정제하였다. 합성한 각 전구체를 ICI 담체를 이용하여 높은 수율로 표지하였고, HPLC를 사용하여 분리하였다. Radiohalogen exchange 방법은 비방사능을 낮게 할수록 표지에 효율적으로 알려져 있다. 이 방법으로 ICI 방법을 사용하여 담체를 포함하는 높은 방사능의 화합물을 얻을 수 있다. 결과: IVDU와 IVFRU 표지를 위한 전구체 합성수율은 각각 43, 72% 였다. ICl로 담체를 이용한 표지방법을 사용하여 IVDU와 IVFRU 표지수율은 98% 이상이었다. 결론: HSV1-tk를 이용한 유전자 영상용 기질의 전구체를 성공적으로 합성하였고. 95% 이상의 높은 표지수율의 유전자 영상용 방사성 추적자를 성공적으로 제조하였다.

• Archives of Pharmacal Research
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• 제20권1호
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• pp.58-67
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• 1997

In order to find antiviral compounds against Herpes simplex virus type I (HSV-1) and II (HSV2) from natural products, a convenient virus-induced cytopathic effect (CPE) inhibition assay was introduced. More than 300 fractions were prepared by solvent fractionation from sixty collected plants or purchased herbal medicines, and their anti-herpetic activities were evaluated. Among them, several medicinal plants showed potent anti-herpetic activity. Selective indexes (SI) of the EtOAc extract of Caraganae Radix (Caragana sinica) against HSV-1 and HSV-2 were more than 8.06 and 24.79, SI of the MeOH extract of Acer okamotoanum leaves were 3.92 and 3.51, SI of the $CH_{2}Cl_{2}$ extract of Veratri Rhizoma et Radix (Veratrum patulum) were 5.49 and 1.31 and SI of the MeOH extract of aerial part of Osmundae Rhizoma (Osmunda japonica) were more than 3.45 and 1.25, respectively.

• Biomolecules & Therapeutics
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• 제1권1호
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• pp.98-102
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• 1993

The therapeutic effectiveness of adenine arabinoside(tora-A) and its conjugate of prednisone(BR-8702-AP) was compared in Herpes simplex Virus Type 1 (HSV-1) infected BALB/C mice. The BALB/C mouse was infected with HSV-1(700 PFU/mouse) intranasally. Among mice infected intranasally with virus, a mortality rate of 100% was observed. On the oral administration of non-toxic doses of ara-A or BR-8702-AP(125 mg /kg/day) for 5 consecutive days 2 hours after virus infection, the tora-A was highly effective in reducing mortality to 0% (P<0.001) and BR-8702-AP was also effective in reducing mortality to 15% (P<0.01). In this model infection, the virus was first replicated in the lung and transmitted to the brain. Both arts-A and BR-8702-AP did not inhibit the viral replication in the lung, but they inhibited the viral transmission to the brain. However, the BR-8702-AP was less effective than the aria-A to prevent transmission of virus to brain. Therefore, the reduced mortality due to tora-A or BR-8702-AP therapy was associated with inhibition of viral transmission to brain.

• 대한약리학회지
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• 제28권2호
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• pp.213-222
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• 1992

Benzopyrene (BP), 7,12-dimehyl benzanthracene (DMBA), nitrosomethyl urea (NUMU) 및 nicotine과 같은 발암성 화학물질들이 바이러스 감염된 vero 세포의 단층 세포 배양에서 I형 단순성포진 바이러스 (HSV-1)의 복제, 세포융해, DNA합성 및 단백질 합성에 미치는 효과를 관찰하였다. 1. BP와 DMBA는 HSV-1의 복제와 세포융해작용을 유의성있게 억제하였으나 nicotine과 NMU는 별로 억제하지 않았다. 2. 모든 발암성 화학물질은 바이러스의 DNA합성을 억제하지 못하였지만 새로 합성되는 후손바이러스 DNA로 부터 표현되는 gamma 단백질의 표현은 BP와 DMBA에 의해서 현저하게 억제되었다. 그러나 모든 발암성 화학물질은 바이러스의 alpha 및 beta 단백질의 합성은 억제하지 못하였다. 이상의 결과로 보아 발암성화학물질이 존재하고 있는 배지내에서 새로 합성되는 바이러스의 DNA로 부터 표현되는 gamma 단백질의 결함이 있음을 알 수가 있었으며 이같은 개념은 발암화학물질의 존재하에서 바이러스의 DNA와 단백질이 거의 정상적으로 합성됨에도 불구하고 바이러스의 복제가 일어나지 않는다는 사실이 뒷받침해주고 있다.

• Journal of Microbiology and Biotechnology
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• 제28권6호
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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.

• 대한바이러스학회지
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• 제29권4호
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• pp.283-288
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• 1999

Zosteriform lesions, occurring after left flank and intravaginal inoculations of Balb/c mice with the Herpes simplex virus type 1 strain McKrae, developed in clinically normal skin via nerve endings. The developments of zosteriforms were standardized in 5 phases with the following references; formation of small vesicles (phase 1); occurrence of erosion and ulceration of local lesions (phase 2); occurrence of ulcerations (phase 3); occurrence of severe ulcerations (phase 4); and death (phase 5). These results provide two valuable zosteriform models to further investigate and analyze the pathological symptoms in susceptible animals infected with HSV-1 or HSV-2 and DNA vaccines.

• Bulletin of the Korean Chemical Society
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• 제30권2호
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• pp.435-440
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• 2009

19 Aromatic ring and L-amino acid ester contained rupestonic acid amide derivatives 2a~2l, 3a~3g were synthesized and preliminarily evaluated in vitro against influenza virus $A_3$,B and herpes simplex virus type 1 (HSV-1), 2(HSV-2) by the national center for drug screening of China. The rusults showed that 2i possessed the highest inhibition against both influenza virus $A_3\;(TC_{50}\;=\;120.6\;{\mu}mol/L,\;IC_{50}=\;19.2\;{\mu}$mol/L, SI = 6.3) and B (T$C_{50}\;=\;120.6\;{\mu}mol/L,\;IC_{50}=\;29.9\;{\mu}$mol/L, SI = 4.0); 2g was more active against influenza $A_3$ virus at very low cytotoxicity ($TC_{50}\;>\;2092.1\;{\mu}mol/L,\;IC_{50}=\;143.7\;{\mu}mol/L,$ SI > 14.6) than the parent compound; Compounds 2b, 2c, 2f showed higher activities both against HSV-1 and HSV-2 than that of the parent compound, and 2f was the most potent inhibitor of HSV-1 ($TC_{50}\;=\;200.0\;{\mu}mol/L,\;IC_{50}\;=\;11.3\;{\mu}mol$/L, SI = 17.7 ) and HSV-2 ($TC_{50}\;=\;200.0\;{\mu}mol/L,\;IC_{50}\;=\;20.7\;{\mu}mol$/L , SI = 9.7).

• 미생물학회지
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• 제42권3호
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• pp.177-184
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• 2006

항구 도시인 부산의 바이러스성 성병 감염 현황과 고위험군 지표로서 HPV, HSV 및 HBV 감염자의 성별, 연령대별 유형율 조사 등 기초자료를 확보하여 성매개감염증 사업관리 및 전파방지에 중요한 자료를 제공하고자 한다. 자궁경부도찰물 674건 중 HPV 23건(3.4%)과 HSV 1 2형 3건(0.4%) 9건(1.3%)이 각각 분리되었으며, 혈청 586건 중 HSV IgM 121건(3.6%), HSV-1 IgG 487건(83.1%), HSV-2 IgG 135건(23.0%), HBsAg 26건(4.4%), HBeAg 7건 (1.2%) 등이 검출되었다. HPV 유전자형별 분포도는 고위험군이 15종(13명), 저위험군이 6종(3명)으로 나타났으며, 복합감염은 7명이었다. 연령별 발생분포는 자궁경부도찰물의 경우 20대 이하가 24건(7.2%), 혈청의 경우 40대 이상이 101건(100%)으로 가장 높았다. 그리고 업소별 분포도는 자궁경부도찰물에서 보건소의 검진대상자(유흥업소종사자)들이 감염율이 가장 높았고, 혈청에서는 대용성병진료소의 검진대상자(특수업태부)가 감염율이 가장 높았다.