University of Minnesota Medical School, Center for Infectious Diseases and Microbiology Translational Research, 2001 6th Street SE, MN 55455, USA.
Expert Opin Drug Metab Toxicol. 2011 Oct;7(10):1245-65. doi: 10.1517/17425255.2011.613824. Epub 2011 Sep 1.
Cytomegalovirus (CMV) is a ubiquitous pathogen that establishes a lifelong asymptomatic infection in healthy individuals. Infection of immunesuppressed individuals causes serious illness. Transplant and AIDS patients are highly susceptible to CMV leading to life-threatening end-organ disease. Another vulnerable population is the developing fetus in utero, where congenital infection can result in surviving newborns with long-term developmental problems. There is no vaccine licensed for CMV and current antivirals suffer from complications associated with prolonged treatment. These include drug toxicity and emergence of resistant strains. There is an obvious need for new antivirals. Candidate intervention strategies are tested in controlled preclinical animal models but species specificity of human CMV precludes the direct study of the virus in an animal model.
This review explores the current status of CMV antivirals and development of new drugs. This includes the use of animal models and the development of new improved models such as humanized animal CMV and bioluminescent imaging of virus in animals in real time.
Various new CMV antivirals are in development, some with greater spectrum of activity against other viruses. Although the greatest need is in the setting of transplant patients, there remains an unmet need for a safe antiviral strategy against congenital CMV. This is especially important as an effective CMV vaccine remains an elusive goal. In this regard, greater emphasis should be placed on suitable preclinical animal models and greater collaboration between industry and academia.
巨细胞病毒(CMV)是一种普遍存在的病原体,它在健康个体中建立终生无症状感染。免疫抑制个体感染会导致严重疾病。移植和艾滋病患者极易感染 CMV,导致危及生命的终末器官疾病。另一个易受感染的人群是子宫内发育中的胎儿,先天性感染可导致存活新生儿出现长期发育问题。目前尚无获准用于 CMV 的疫苗,而现有的抗病毒药物存在与长期治疗相关的并发症。这些包括药物毒性和耐药株的出现。显然需要新的抗病毒药物。候选干预策略在受控的临床前动物模型中进行了测试,但人类 CMV 的物种特异性排除了在动物模型中直接研究该病毒的可能性。
本综述探讨了 CMV 抗病毒药物的现状和新药的开发。这包括使用动物模型以及开发新的改进模型,如人源化动物 CMV 和实时动物体内病毒的生物发光成像。
各种新的 CMV 抗病毒药物正在开发中,其中一些具有针对其他病毒更大的活性谱。尽管最大的需求是在移植患者中,但仍需要针对先天性 CMV 的安全抗病毒策略。这一点尤其重要,因为有效的 CMV 疫苗仍然是一个难以实现的目标。在这方面,应更加重视合适的临床前动物模型,并加强工业界和学术界之间的合作。