Department of Molecular Genetics and Microbiology, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32610, USA.
Viruses. 2011 Jan;3(1):47-62. doi: 10.3390/v3010047.
CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Previously, we demonstrated the efficacy of CMX001 in protecting New Zealand White rabbits from mortality following intradermal infection with rabbitpox virus as a model for smallpox, monkeypox and for treatment of adverse reactions to smallpox vaccination. Here we extend these studies by exploring different dosing regimens and performing randomized, blinded, placebo-controlled studies. In addition, because rabbitpox virus can be transmitted via naturally generated aerosols (animal to animal transmission), we report on studies to test the efficacy of CMX001 in protecting rabbits from lethal rabbitpox virus disease when infection occurs by animal to animal transmission. In all cases, CMX001 treatment was initiated at the onset of observable lesions in the ears to model the use of CMX001 as a treatment for symptomatic smallpox. The results demonstrate that CMX001 is an effective treatment for symptomatic rabbitpox virus infection. The rabbitpox model has key similarities to human smallpox including an incubation period, generalized systemic disease, the occurrence of lesions which may be used as a trigger for initiating therapy, and natural animal to animal spread, making it an appropriate model.
CMX001 是一种通过将 3-(己癸氧基)丙醇与更昔洛韦（CDV）共价连接而形成的亲脂性核苷酸类似物，正在被开发用于治疗天花。由于没有人类天花病例，新的治疗方法必须在动物模型中进行疗效测试。此前，我们证明了 CMX001 能够保护新西兰白兔免受兔痘病毒经皮感染后的死亡率，作为天花、猴痘的模型，并用于治疗天花疫苗接种的不良反应。在这里，我们通过探索不同的剂量方案并进行随机、盲法、安慰剂对照研究来扩展这些研究。此外，因为兔痘病毒可以通过自然产生的气溶胶（动物对动物传播）传播，我们报告了研究 CMX001 对通过动物对动物传播感染致死性兔痘病毒疾病的保护作用的研究。在所有情况下，CMX001 治疗都是在耳朵出现可见病变时开始的，以模拟 CMX001 作为治疗有症状天花的用途。结果表明，CMX001 是一种治疗有症状兔痘病毒感染的有效方法。兔痘模型与人天花有许多关键相似之处，包括潜伏期、全身性疾病、病变的发生，这些病变可以作为启动治疗的触发因素，并且可以自然地在动物之间传播，使其成为一种合适的模型。
