Antivirals and antiviral strategies.
Antivirals and antiviral strategies.
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DOI：
10.1038/nrmicro975
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发表时间：
2004-09
期刊：
影响因子：
--
通讯作者：
De Clercq E
中科院分区：
文献类型：
--
作者：
De Clercq E
在这篇文章中，有用的，或潜在的有用性，目前许可的抗病毒药物和那些在临床或临床前的发展进行了评估。主要结论如下：对于多瘤病毒、乳头瘤病毒、腺病毒和痘病毒感染的治疗，无环核苷膦酸酯如西多福韦具有最大的潜力。对于HSV和VZV感染的治疗，（瓦尔）阿昔洛韦、泛昔洛韦和溴夫定是重要的。对于CMV感染的治疗，（瓦尔）更昔洛韦、西多福韦和膦甲酸是最有希望的。利巴韦林被提议用于治疗（-）RNA病毒（例如沙粒病毒和布尼亚病毒）感染，而IFN和IFN诱导剂被设想用于治疗（+）RNA病毒感染，特别是小核糖核酸病毒（例如科萨基B）和披膜病毒（例如，西方、东方和委内瑞拉马脑炎病毒）感染。对于HCV感染的治疗，目前推荐聚乙二醇化IFN与利巴韦林组合，尽管也已经开发了靶向HCV蛋白酶和RNA依赖性RNA聚合酶的化合物。对于流感病毒感染的治疗和预防，神经氨酸酶抑制剂扎那米韦和奥司他韦是目前的首选药物。在副粘病毒中，人偏肺病毒（hMPV）和呼吸道合胞病毒（RSV）是最需要抗病毒治疗的病毒。虽然利巴韦林可用于治疗RSV感染，但它并不理想，因此需要新的化合物来治疗hMPV和RSV感染。大量的“旧”和“新”化合物可用于或正在开发用于治疗HIV感染。多种药物方案可能对艾滋病毒治疗有益。对于其他病毒感染-轮状病毒和埃博拉病毒、马尔堡病毒和其他出血性病毒感染-潜在抗病毒剂的选择相当有限，然而，SAH水解酶抑制剂如3-去氮普兰诺菌素A目前是最有希望的。本文的在线版本（doi：10.1038/nrmicro 975）包含补充材料，可供授权用户使用。近年来，对新的抗病毒策略的需求显著增加。导致需求增加的因素有很多，包括艾滋病毒、B型和C型肝炎等慢性病毒感染的流行率不断上升，以及SARS冠状病毒等新病毒的出现。出血热病毒和天花病毒等已被根除的病毒被用作生物恐怖主义武器的潜在危险也增加了抗病毒药物发现的重要性。在这里，需要抗病毒治疗的病毒感染和可用的或正在开发的用于治疗这些感染的化合物被描述。本文的在线版本（doi：10.1038/nrmicro 975）包含补充材料，可供授权用户使用。
In this article, the usefulness, or potential usefulness, of the currently licensed antiviral drugs and those in clinical or preclinical development is evaluated. The main conclusions are: For the treatment of polyomavirus, papillomavirus, adenovirus and poxvirus infections, the acyclic nucleoside phosphonates such as cidofovir have the greatest potential. For the treatment of HSV and VZV infections, (val)acyclovir, famciclovir and brivudin are important. For the treatment of CMV infections, (val)ganciclovir, cidofovir and foscarnet are the most promising. Ribavirin is proposed for the treatment of (−)RNA virus (such as arenavirus and bunyavirus) infections, whereas IFN and IFN inducers are envisaged for the treatment of (+)RNA virus infections, particularly picornavirus (for example, coxsackie B) and togavirus (for example, Western, Eastern and Venezuelan equine encephalitis virus) infections. For the treatment of HCV infections, pegylated IFN, in combination with ribavirin, is currently recommended, although compounds targeted at the HCV protease and RNA-dependent RNA polymerase have also been developed. For the therapy and prophylaxis of influenza virus infections, the neuraminidase inhibitors zanamivir and oseltamivir are the current drugs of choice. Among the paramyxoviruses, human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are the viruses for which antiviral therapy is most required. Although ribavirin is available for the treatment of RSV infections, it is not ideal, and therefore, new compounds are required for the treatment of hMPV and RSV infections. A plethora of 'old' and 'new' compounds are available or are being developed for the treatment of HIV infections. Multiple drug regimens might be beneficial for HIV treatment. For other virus infections —rotavirus, and Ebola, Marburg and other haemorrhagic virus infections — the choice of potential antiviral agents is rather limited, however, SAH hydrolase inhibitors such as 3-deazaneplanocin A are currently the most promising. The online version of this article (doi:10.1038/nrmicro975) contains supplementary material, which is available to authorized users. In recent years, the demand for new antiviral strategies has increased markedly. There are many contributing factors to this increased demand, including the ever-increasing prevalence of chronic viral infections such as HIV and hepatitis B and C, and the emergence of new viruses such as the SARS coronavirus. The potential danger of haemorrhagic fever viruses and eradicated viruses such as variola virus being used as bioterrorist weapons has also increased the profile of antiviral drug discovery. Here, the virus infections for which antiviral therapy is needed and the compounds that are available, or are being developed, for the treatment of these infections are described. The online version of this article (doi:10.1038/nrmicro975) contains supplementary material, which is available to authorized users.
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