Poxvirus Team, Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
J Virol. 2011 Sep;85(17):9176-87. doi: 10.1128/JVI.02173-10. Epub 2011 Jun 22.
Smallpox preparedness research has led to development of antiviral therapies for treatment of serious orthopoxvirus infections. Monkeypox virus is an emerging, zoonotic orthopoxvirus which can cause severe and transmissible disease in humans, generating concerns for public health. Monkeypox virus infection results in a systemic, febrile-rash illness closely resembling smallpox. Currently, there are no small-molecule antiviral therapeutics approved to treat orthopoxvirus infections of humans. The prairie dog, using monkeypox virus as a challenge virus, has provided a valuable nonhuman animal model in which monkeypox virus infection closely resembles human systemic orthopoxvirus illness. Here, we assess the efficacy of the antiorthopoxvirus compound ST-246 in prairie dogs against a monkeypox virus challenge of 65 times the 50% lethal dose (LD(50)). Animals were infected intranasally and administered ST-246 for 14 days, beginning on days 0, 3, or after rash onset. Swab and blood samples were collected every 2 days and analyzed for presence of viral DNA by real-time PCR and for viable virus by tissue culture. Seventy-five percent of infected animals that received vehicle alone succumbed to infection. One hundred percent of animals that received ST-246 survived challenge, and animals that received treatment before symptom onset remained largely asymptomatic. Viable virus and viral DNA were undetected or at greatly reduced levels in animals that began treatment on 0 or 3 days postinfection, compared to control animals or animals treated post-rash onset. Animals treated after rash onset manifested illness, but all recovered. Our results indicate that ST-246 can be used therapeutically, following onset of rash illness, to treat systemic orthopoxvirus infections.
天花的备灾研究促成了抗病毒疗法的发展，用于治疗严重的正痘病毒感染。猴痘病毒是一种新兴的人畜共患正痘病毒，可导致人类严重且具有传染性的疾病，引发人们对公共卫生的担忧。猴痘病毒感染会导致全身性发热皮疹疾病，与天花非常相似。目前，尚无批准用于治疗人类正痘病毒感染的小分子抗病毒疗法。草原犬鼠可用作猴痘病毒的挑战病毒，为研究猴痘病毒感染提供了一种非常有价值的非人类动物模型，其感染与人系统性正痘病毒疾病非常相似。在这里，我们评估了抗正痘病毒化合物 ST-246 在草原犬鼠中的疗效，以应对 65 倍 50%致死剂量（LD(50)）的猴痘病毒挑战。动物经鼻腔感染，并在 0、3 天或出疹后开始接受 ST-246 治疗 14 天。每 2 天采集拭子和血液样本，通过实时 PCR 分析存在病毒 DNA，通过组织培养分析存在活病毒。单独接受载体的 75%感染动物死亡。接受 ST-246 的动物 100%存活，且在症状出现前接受治疗的动物基本上无症状。与对照动物或出疹后开始治疗的动物相比，在感染后 0 天或 3 天开始治疗的动物中，活病毒和病毒 DNA 未被检测到或大大减少。出疹后开始治疗的动物出现疾病，但均康复。我们的结果表明，在出疹性疾病出现后，ST-246 可作为治疗药物，用于治疗系统性正痘病毒感染。
