Department of Pediatrics, School of Medicine, The University of Alabama, 170 Children's Harbor Building, 1600 6th Avenue South, Birmingham, Birmingham, AL 35233, USA; E-Mail:
Viruses. 2010 Dec;2(12):2681-95. doi: 10.3390/v2122681. Epub 2010 Dec 13.
Although a large number of compounds have been identified with antiviral activity against orthopoxviruses in tissue culture systems, it is highly preferred that these compounds have activity in vivo before they can be seriously considered for further development. One of the most commonly used animal models for the confirmation of this activity has been the use of mice infected with either vaccinia or cowpox viruses. These model systems have the advantage that they are relatively inexpensive, readily available and do not require any special containment facilities; therefore, relatively large numbers of compounds can be evaluated in vivo for their activity. The two antiviral agents that have progressed from preclinical studies to human safety trials for the treatment of orthopoxvirus infections are the cidofovir analog, CMX001, and an inhibitor of extracellular virus formation, ST-246. These compounds are the ones most likely to be used in the event of a bioterror attack. The purpose of this communication is to review the advantages and disadvantages of using mice infected with vaccinia and cowpox virus as surrogate models for human orthopoxvirus infections and to summarize the activity of CMX001 and ST-246 in these model infections.
虽然在组织培养系统中已经鉴定出大量具有抗正痘病毒活性的化合物，但在这些化合物可以被认真考虑进一步开发之前，它们在体内具有活性是非常重要的。最常用于确认这种活性的动物模型之一是使用感染牛痘或牛痘病毒的小鼠。这些模型系统具有相对便宜、易于获得且不需要任何特殊隔离设施的优点；因此，可以在体内评估相对大量的化合物以评估其活性。已经从临床前研究进展到人类安全试验以治疗正痘病毒感染的两种抗病毒药物是cidofovir 类似物 CMX001 和细胞外病毒形成抑制剂 ST-246。这些化合物是在发生生物恐怖袭击时最有可能使用的药物。本通讯的目的是综述使用感染牛痘和牛痘病毒的小鼠作为人正痘病毒感染替代模型的优缺点，并总结 CMX001 和 ST-246 在这些模型感染中的活性。
