Treatments for Nipah Virus Infection

我们将开发一种感染尼帕病毒(Nipah Virus，NIV)的非洲绿猴模型，并对其进行全面表征 将使用这一模型来评估现有的治疗新城疫病毒感染的治疗方法。 该提案通过关注由以下项目确定的关键研究差距来实现RCE计划的使命 NIAID包括： 1)研究较少的NIAID A-C类药物的基础生物学； 2)发病机制，侧重于研究较少的因素； 3)治疗学的目标识别； 4)用于发病机制研究和治疗评价的新动物模型的建立。 此外，该提案寻求采用广谱方法来治疗埃尼帕病毒的一个主要特征。 感染(急性呼吸窘迫综合征[ARDS])以改善预后。由于ARDS是一种 其他新出现的传染病的显著特征这种方法可能有更多的用处 埃尼帕病毒。 明确的目标。 在目标1中，我们将在非洲绿中建立新城疫病毒的感染、致死量和检测参数 猴子模型。 在目标2中，我们将确定现有药物利巴韦林对非洲新城疫病毒的保护效果。 绿猴子。 在目标3中，我们将确定中和的、抗G的、全人单抗的被动保护效果。 非洲绿猴新城疫病毒感染的抗体治疗。 在目标4中，我们将确定新城疫病毒感染中ARDS的机制，并评估广谱分析的能力 抗凝剂，以减轻ARDS的有害后果。

We will develop and fully characterize an African green monkey model of Nipah virus (NiV) infection and we will use this model to evaluate existing and discover new therapeutic modalities for treating NiV infection. This proposal addresses the mission of the RCE program by focusing on critical research gaps identified by NIAID including: 1) basic biology of less well-studied NIAID Category A-C agents; 2) mechanisms of pathogenesis, with emphasis on less well-studied agents; 3) target identification for therapeutics; and 4) development of new animal models for pathogenesis studies and therapeutics evaluation. In addition, the proposal seeks to employ a broad-spectrum approach to treat a major feature of henipavirus infection (acute respiratory distress syndrome [ARDS]) in order to improve outcome. As ARDS is a prominent feature of other emerging infectious diseases this approach may have utility beyond henipaviruses. SPECIFIC AIMS. In Aim 1, we will establish virus infection, lethal dose, and detection parameters of NiV in an African green monkey model. In Aim 2, we will determine the protective efficacy of the existing drug ribavirin against NiV in the African green monkey. In Aim 3, we will determine the passive protective efficacy of neutralizing, anti-G, fully-human monoclonal antibody therapy for NiV infection in the African green monkey. In Aim 4, we will determine the mechanism of ARDS seen in NiV infections and evaluate the ability of broadspectrum anticoagulants to ameliorate the deleterious consequences of ARDS.