喷昔洛韦栓的制备及质量控制

喷昔洛韦（penciclovir，PCV）是英国SKB公司开发的开环核苷类抗病毒药物，是前体药物泛昔洛韦（famciclovir，FCV）的代谢产物，有抗单纯疱疹病毒HSV—Ⅰ，HSV—Ⅱ，VZV（带状疱疹）和EB病毒的作用，它的作用机制与阿昔洛韦相似，与阿昔洛韦相比，其抗病毒效果显著，是一种抗病毒谱较广的药物。主要用于治疗单纯疱疹病毒引起的感染，也可用于治疗带状疱疹病毒感染。     

核苷类抗病毒药物研究进展

近年来新的抗病毒药物不断出现,但病毒性感染的发病率仍持续不衰,特别是80年代初艾滋病及其原病毒的出现,对抗病毒药物的研究开发提出了紧迫的要求.由于人类免疫缺陷病毒( HIV)感染病人往往对其他病毒感染很敏感,如单纯疱疹病毒(HSV)、巨细胞病毒(CMV)、水痘带状疱疹病毒(VZV)等等.因此,治疗HIV感染的同时也要给予抗这些病毒的药物,这样就进一步推动了抗病毒药物的发展.     

空心莲子草有效部份抗病毒作用的实验研究

<正> 我们在进行空心莲子草抗病毒研究时,发现它在细胞培养中对单纯疱疹病毒(HSV)有抑制作用。用铅盐沉淀法将空心莲子草分成三个部分,在Hep-2细胞系统进行抗HSV研究。以感染细胞内HSV有无抑制作为药物的疗效观察指标,病毒的感染性滴度下降2个对数单位作为药物的有效抑制浓度。首先将三个部份以20、40、80、100、200、400、800和2000     

单纯疱疹病毒:免疫接种之利弊因素

欲评价抗疱疹病毒感染免疫接种之利弊,应对该感染的生物学作必要的分析。单纯疱疹病毒(HSV)按其血清学、生物化学和生物学特征分为两个型别:1型HSV(HSV 1)主要引起口腔局部感染,也是引起疱疹性角膜炎的病毒;2型HSV(HSV 2)经性生     

生殖器疱疹及其疫苗的研究进展

生殖器疱疹由单纯疱疹病毒（herpes simplex virus,HSV）感染所致,在世界范围内广泛流行。HSV可在宿主体内建立终身潜伏感染,并引起严重的复发性疾病。此外,HSV感染还能明显增加HIV感染的机率。虽然目前抗HSV药物有一定作用,但是不能防止潜伏HSV复活。因此, 亟需研制有效的疫苗来控制HSV感染、限制疾病传播和复发。此文对生殖器疱疹的病原学、流行病学及疫苗的研究进展做一综述。     

空心莲子草在体外对单纯疱疹病毒的抑制作用

本文报道空心莲子草在细胞培养中对单纯疱疹病毒(HSV)的抑制作用。以间接免疫荧光法检查HSV感染的细胞内HSV有无抑制作为观察药物抗病毒作用的指标。研究结果表明该药有两个部份能抑制HSV—1型在细胞培养中繁殖,抑制浓度为200μg/ml和100μg/ml;就抗HSV—2型而言,该药的3个部份均有效,抑制浓度分别为40μg/ml、40μg/ml和80μg/ml。该药对病毒吸附细胞无干扰作用。以上结果说明空心莲子草对HSV的抑制作用与它的部份有关。因此,提取和人工合成中草药的有效部份是研制中药的重要内容。本试验也说明这种药物用于HSV感染的治疗是有希望的。     

喷昔洛韦（Penciclovir）小针及输液剂

喷昔洛韦(penciclovir，PCV)是英国SKB公司开发的开环核苷类抗疱疹病毒药，是前体药物泛昔洛韦(famciclovir，famir，FCV)的代谢产物。化学名为9-[4-羟基-3-(羟甲基)丁基卜鸟嘌吟。其乳膏剂于1996年6月在英国首获上市，粉针剂也于1998年上市。本品有抗单纯疱疹病毒HSV—Ⅰ、HSV—Ⅱ、VZV(带状疱疹)和EB病毒的作用。在病毒感染细胞中，病毒胸腺嘧啶脱氧核苷激酶将本品磷酸化为喷昔洛韦单磷酸盐，     

灵芝中酸性蛋白结合多糖单用或与阿昔洛韦和阿糖腺苷合用的抗疱疹病毒活性

为寻找抗疱疹病毒活性成分,作者以生物活性为指导,从灵芝子实体水溶性物质中分得一棕色酸性蛋白结合多糖(APBP)。抗单纯疱疹病毒Ⅰ型(HSV-1)和Ⅱ型(HSV 2)的实验显示,APBP对Vero细胞中的HSV1和HSV-2均具强抗病毒活性,EC_(50)分别为     

喷昔洛韦与阿昔洛韦治疗豚鼠单纯疱疹的疗效比较

为比较喷昔洛韦 (PCV)与阿昔洛韦 (ACV)对单纯疱疹的疗效 ,建立了豚鼠皮肤单纯疱疹的模型 ,比较不同时间的疗效积分和皮损处 1型单纯疱疹病毒 (HSV - 1)发现 :0 2 %PCV组对疱疹疗效及对HSV - 1抑制作用要比 1%ACV组好 ,表明PCV治疗单纯疱疹的疗效要比ACV好 ,其抗HSV - 1活性也比ACV高     

抗病毒药的耐药性和选药

病毒对抗病素药物产生耐药性的问题越来越被人们所重视.单纯疱疹病毒(HSV)、巨细胞病毒(MV)、水痘带状疱疹病毒(VZV)及流在病毒A(in-fluenza-A)等的感染患者,如用了抗病毒药物治疗后,病情仍难以控制或出现新的损害时,应考虑到耐药性的存在,并立即更换治疗方案,选择适当的替代治疗药物.一些早期的抗病毒药具有令人无法忍受的毒性(如阿糖胞苷和疱疹净),特别是出现三致(致癌、致畸、致突变),因此不能广泛应用.用于预防流感病毒A感染非常有效的金刚烷胺巴也减少应用,1977年阿昔洛韦(acyclovir)的发现,因其对免疫缺陷患者原发及复发的生殖器疱疹、疱疹性脑炎、新生儿疱疹和VZV的感染极为有效而被广泛应用.因此,抗病毒药的耐药性首先出现在那些用阿昔洛韦来治疗的疱疹病毒感染患者中.1 抗疱疹病毒药分类1.1核苷类似物 疱疹净(idoxuridine)、阿糖腺苷     

New advances in anti-HSV chemotherapy

Treatment of human herpes simplex virus (HSV) diseases represents an important goal, as herpetic infections are not controlled by vaccination. Many therapeutic agents have been developed and used for HSV infections and several alternative natural compounds are under investigation. Most of the drugs clinically employed against HSV types 1 and 2 are represented by guanosine nucleoside analogues, such as aciclovir and aciclovir-like drugs. The emergence of aciclovir-resistant virus strains provided a stimulus for increased search of new effective agents. Alternative drugs are other nucleoside analogues, such as the vidarabine, brivudin, and cidofovir, or pyrophosphate analogues such as foscarnet, that showed efficacy for HSV infections refractory to aciclovir. However, the risk of adverse effects reported for available anti-herpetic compounds and the frequent development of drug-resistant strains of HSV following therapeutic treatment generate the need for new antiviral agents. In the last years, several studies have been carried out on the anti-HSV activity of different components of innate host defences such as cationic antimicrobial peptides. The antiviral activity of these peptides often appears to be related to the viral adsorption and entry process or is a result of a direct effect on the viral envelope. Other natural compounds, extracts from medicinal plants employed in ethnomedicine and displaying marked anti-herpetic activity, are at present under investigation to determine the scientific evidence and rationale for their clinical use. This review discusses the anti-HSV activity of compounds licensed for clinical use and promising natural molecules.     

Topical antiviral agents for herpes simplex virus infections

Several antiviral agents against herpes simplex virus (HSV) infection have been clinically studied. Earlier therapies include gluteraldehyde, povidone-iodine, butylated hydroxytoluene and ether. Nucleoside analogs have been tested for efficacy in HSV. Although acyclovir and adenine arabinoside have shown minimal therapeutic benefit, cidofovir has been successful in the treatment of acyclovir-resistant strains of HSV, and idoxuridine 15% in dimethyl sulfoxide, edoxudine and penciclovir have significant clinical benefit against HSV. Interferon-alpha has shown synergism with other anti-HSV drugs such as caffeine, trifluorothymidine, dimethyl sulfoxide and nonoxynol-9, and ascorbic acid shows promising effects against HSV. Using a vehicle that enhances skin penetration of a drug or further exploring combination therapy may result in efficacious treatment of HSV. Vaccination or gene therapy may also prove beneficial in future studies.     

Advances in herpes simplex virus antiviral therapies

Herpes simplex viruses (HSV) are responsible for usually non-life threatening infections of the oral, ocular and genital regions. The viruses infect a significant percentage of the US population and almost two million new cases are reported each year. Present medicinal agents that treat HSV target the catalytic activity of the virally encoded DNA polymerase. Although these agents have been shown to be safe and efficacious, many possess limited oral bioavailability, must be given early in the disease process for maximum effect and resistance to these agents is a significant problem in immunocompromised individuals. Thus, there is the need for continued development of new anti-HSV agents. This review discusses new anti-HSV agents published in the medical and patent literature during 2004 – 2006 and highlights recent advances in the development of nucleoside and non-nucleoside inhibitors of polymerase, inhibitors of the HSV helicase–primase complex, viral entry inhibitors and anti-HSV compounds that have no defined mechanism of action.     

Extracts and molecules from medicinal plants against herpes simplex viruses

Herpes simplex viruses (HSV-1 and -2) are important pathogens for humans, especially in the case of highly susceptible adults. Moreover, HSV-2 has been reported to be a high risk factor for HIV infection. Therefore, the discovery of novel anti-HSV drugs deserves great efforts. In this paper, we review anti-HSV substances from natural sources, including both extracts and pure compounds from herbal medicines, reported in studies from several laboratories. The role of traditional medicine for the development of anti-HSV compounds is also discussed. Interestingly, it was found that traditional medicines, like Ayurvedic, traditional Chinese (TCM), Chakma medicines, are good and potential sources for promising anti-HSV drugs. A second objective of this review is to discuss several anti-HSV compounds with respect to their structure-activity relationship (SAR). A large number of small molecules, like phenolics, polyphenols, terpenes (e.g., mono-, di-, tri-), flavonoids, sugar-containing compounds, were found to be promising anti-herpetic agents. Our major conclusion is that natural products from medicinal plant extracts are very important source of anti-HSV agents.     

Inhibitory effect and structure–activity relationship of some Biginelli-type pyrimidines against HSV-1

Inevitable emergence of multi-drug resistant strains to current available drugs makes an impetus for finding new therapeutic agents against herpes simplex virus (HSV). In this study, a series of novel derivatives of Biginelli-type pyrimidines were evaluated as potential anti-HSV-1 compounds by plaque reduction method. The cellular toxicity was assessed by XTT proliferation assay. The time course of anti-HSV activity of the most active compound was studied to show the anti-viral effect in various intervals of replication cycle. Compounds 2, 6, 8, 11, 12, 17, 18, 20, and 40 had the highest activity for inhibition of HSV. Compound 40 inhibited HSV replication with IC₅₀ of 0.9 μmol/l and had CC₅₀ of up to 100 μmol/l. This compound was a noteworthy inhibitor against HSV with TI value of 111. Compound 20 also showed considerable inhibitory activity with IC₅₀ of 1.8 μmol/l. Result of time-of-addition study showed that compound 40 inhibits HSV replication at a stage after entry of virions to the target cells. Analysis of structure of the studied compounds demonstrated clear relationships with their anti-HSV effects. Some of the compounds seem to be promising candidates for future anti-HSV drug discovery researches. Structural manipulation based on the obtained structure–activity relationships would propose some new leads for anti-HSV drug discovery programs.     

Novel targets for the development of anti-herpes compounds

Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are members of the Herpesviridae family. HSV infections have been known since ancient times and are one of the most common communicable diseases in humans. Although infections are often subclinical, HSV can cause mild to severe diseases, especially in immunocompromised patients. Herpes simplex viruses establish latency in the nuclei of neuronal cells and may reactivate, with or without symptoms, throughout the host's lifetime. Over one third of the world's population suffer from recurrent HSV infections several times a year and are thus capable of transmitting HSV by close personal contact. There are few drugs licensed for the treatment of HSV infections. Most target the viral DNA polymerase, and indeed acyclovir remains the reference treatment some thirty years after its discovery! Extensive clinical use of this drug has led to the emergence of resistant viral strains, mainly in immunocompromised patients. This highlights the crucial need for the development of new anti-herpes drugs that can inhibit infection by both wild-type viruses and drug-resistant strains. Over the last few years, significant efforts have been made to set up a range of strategies for the identification of potential new anti-viral drugs. One alternative is to develop drugs with different mechanisms of action. The present article reviews potential viral and cellular targets that are now known to be involved in HSV infection and for which specific inhibitors with anti-HSV activity, at least in cell culture, have been identified.     

Antiviral activities in extracts of Turkish medicinal plants

A total of 16 ethanol extracts of Turkish medicinal plants were evaluated for antiviral activities against herpes simplex virus (HSV) and Sindbis virus (SINV). Extracts of Galanthus elwesii and Rheum ribes showed the most potent anti-HSV activities, while six other extracts had weaker activities. Galanthus elwesii and Leucojum aestivum were the most potent anti-SINV extracts with four others showing weaker activities. In total, five extracts were active against both viruses, three were selective for HSV and one was selective for SINV. Evidence for an antiviral photosensitizer was obtained in two anti-HSV extracts, in which activity was either completely dependent on light, or was con-siderably enhanced by light. Thus, several Turkish medicinal plants appear to be promising sources of antiviral activities.     

Antiviral Activities in Extracts of Turkish Medicinal Plants

A total of 16 ethanol extracts of Turkish medicinal plants were evaluated for antiviral activities against herpes simplex virus (HSV) and Sindbis virus (SINV). Extracts of Galanthus elwesii and Rheum ribes showed the most potent anti-HSV activities, while six other extracts had weaker activities. Galanthus elwesii and Leucojum aestivum were the most potent anti-SINV extracts with four others showing weaker activities. In total, five extracts were active against both viruses, three were selective for HSV and one was selective for SINV. Evidence for an antiviral photosensitizer was obtained in two anti-HSV extracts, in which activity was either completely dependent on light, or was con-siderably enhanced by light. Thus, several Turkish medicinal plants appear to be promising sources of antiviral activities.     

Effects of cytokines and R-837, a cytokine inducer, on UV-irradiation augmented recurrent genital herpes in guinea pigs.

We have recently reported that latently HSV-2-infected guinea pigs exhibit a three- to four-fold increase in recurrent lesions after exposure to ultraviolet radiation (UV), allowing rapid evaluation of antiviral drugs in treating recurrent HSV disease. In this report we examine the effect of alpha interferon (IFN-alpha), interleukin-2 (IL-2), and a cytokine inducer (R-837) on UV-induced recurrent genital herpes. We have previously shown that topical R-837 is a biologic response modifier with no in vitro anti-HSV activity, but with potent anti-HSV activity in vivo due to cytokine induction and enhancement of cell-mediated immune responses. Three-day regimens of intravaginal R-837, or five-day intraperitoneal (i.p.) administration of IFN-alpha or of IL-2 each significantly reduced recurrent genital HSV-2 disease that occurred within 7 days of UV exposure, suggesting that cytokines or cytokine inducers may be useful in the treatment of recurrent HSV disease. This model using ultraviolet radiation to induce recurrent herpes simplex virus infection proved useful in the evaluation of immunoactive agents as putative antiviral drugs.