Watanabe Satoru, Vasudevan Subhash G
Emerging Infectious Diseases Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore, Singapore, 169857.
Methods Mol Biol. 2014;1138:391-400. doi: 10.1007/978-1-4939-0348-1_24.
In vivo evaluation of antiviral compounds can serve as criteria in the drug discovery process for selection of compounds that are suitable to enter late preclinical studies and further development. Dengue virus serotypes 1-4 can infect and replicate in the interferon type I and type II receptor deficient mice (AG129). Here we describe the use of a mouse-adapted dengue 2 virus strain (S221) that has been used to develop a robust lethal model of infection. Treatment with small molecule inhibitors of DENV replication at the time of infection or delayed treatment up to 48 h post infection can result in measurable protection that reflects the efficacy of the tested compound.
抗病毒化合物的体内评估可作为药物发现过程中选择适合进入临床前后期研究及进一步开发的化合物的标准。登革病毒1 - 4型可在I型和II型干扰素受体缺陷小鼠(AG129)中感染并复制。在此,我们描述了一种适应小鼠的登革2病毒株(S221)的使用情况,该病毒株已被用于建立一种强大的致死性感染模型。在感染时用登革病毒复制的小分子抑制剂进行治疗,或在感染后长达48小时进行延迟治疗,均可产生可测量的保护作用,这反映了受试化合物的疗效。