Treatments for Nipah Virus Infection

我们将开发并充分表征尼帕病毒（NiV）感染的非洲绿色猴模型， 将使用该模型来评估现有的和发现新的治疗NiV感染的治疗方式。 该提案通过关注以下方面确定的关键研究差距来解决RCE计划的使命： NIAID包括： 1)研究较少的NIAID A-C类病原体的基础生物学; 2)发病机制，重点是研究较少的药物; 3)用于治疗剂的靶标鉴定;以及 4)开发新的动物模型用于发病机制研究和治疗评价。 此外，该建议寻求采用广谱方法来治疗亨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。因为ARDS是一种 其他新出现的传染病的一个突出特点，这种方法可能具有超越 亨尼帕病毒。 具体目标。 在目标1中，我们将建立非洲绿色中NiV的病毒感染、致死剂量和检测参数 猴子模型 在目标2中，我们将确定现有药物利巴韦林在非洲人中对NiV的保护作用。 绿色猴子。 在目标3中，我们将确定中和、抗G、全人单克隆抗体的被动保护功效。 非洲绿色猴NiV感染的抗体治疗。 在目标4中，我们将确定NiV感染中所见的ARDS的机制，并评估广谱免疫治疗的能力。 抗凝血剂以改善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.