Antiviral Drugs for Category A Arenavirus

描述(申请人提供)：生物恐怖主义威胁最高的病原体，A类制剂，如果以不良方式使用，最有可能对公共卫生造成不利影响和造成大量人员伤亡。在A类病毒中，有五种出血热病毒(拉萨病毒、朱宁病毒、马丘波病毒、瓜纳里托病毒和萨比亚病毒)。目前，还没有被批准用于治疗出血热的特定抗病毒药物。我们ArenaVirus抗病毒计划的总体目标是推动至少一种小分子抗病毒药物通过FDA的批准，用于治疗和预防由A类ArenaVirus引起的病毒性出血热，该药物将是安全、有效的，并以胶囊、片剂或液体的形式口服用于治疗、暴露后预防和预防应用。该SBIR第二阶段arenaVirus项目的目标是将在SBIR第一阶段工作中发现的早期arenaVirus特异性抗病毒化合物推进到化学优化中，通过动物功效、启用IND的毒理学和其他临床前活动，我们将提交IND申请的临床开发阶段候选人。人体安全性和药代动力学研究超出了第二阶段工作计划的范围。在这项为期3年的SBIR第二期禽流感病毒计划结束时，我们预计将至少提交一份IND申请，申请一种用于治疗和预防A类禽流感病毒感染的抗病毒候选药物，并确定至少一种额外的ArenaVirus临床前候选药物。针对阿拉伯病毒的抗病毒药物的供应将起到重要的威慑和防御作用，防止在潜在的生物恐怖袭击中使用A类阿拉伯病毒，从而满足国家和全球的安全需要。抗病毒药物可随时储存，并在发生阿拉伯病毒暴发时迅速部署。由于抗病毒药物很容易服用(口服药丸或液体)，并迅速发挥抗病毒作用(在服用后数小时内)，它们将有助于有效地治疗疾病患者，保护那些疑似接触病原体的人(暴露后预防)，并有助于及时控制疫情。

DESCRIPTION (provided by applicant): The highest bioterrorism threat pathogens, the Category A agents, have the greatest potential for adverse public health impact and mass casualties if used in ill-intentioned ways. Among the Category A viruses, there are five hemorrhagic fever arenaviruses (Lassa, Junin, Machupo, Guanarito and Sabia viruses). Currently, there are no specific antiviral treatments approved for use against arenavirus hemorrhagic fevers. The overall goal of our arenavirus antiviral program is to advance through FDA approval at least one small molecule antiviral drug for treatment and prevention of viral hemorrhagic fever due to Category A arenaviruses that will be safe, effective and orally administered as a capsule, tablet or liquid for treatment, post-exposure prophylactic and prophylactic applications. The objective of this SBIR Phase II Arenavirus project is to advance the early stage arenavirus-specific antiviral compounds discovered during our SBIR Phase I work into chemical optimization, through animal efficacy, IND-enabling toxicology and other preclinical activities, to clinical development stage candidates for which we will submit IND applications. Human safety and pharmacokinetic studies are beyond the scope of the Phase II work plan. At the end of this 3-year SBIR Phase II Arenavirus program, we anticipate that we will submit at least one IND application for an antiviral drug candidate for the treatment and prevention of Category A arenavirus infections and identify at least one additional arenavirus preclinical candidate. The availability of arenavirus-specific antiviral drugs will address national and global security needs by acting as significant deterrents and defenses against use of the Category A arenaviruses in potential bioterrorist attacks. Antiviral drugs may be readily stockpiled and rapidly deployed in the event of an arenavirus outbreak. Since antiviral drugs are easily administered (oral pill or liquid) and exert their antiviral effect rapidly (within hours of administration), they will serve to effectively treat diseased patients, protect those suspected of being exposed to the pathogen (post-exposure prophylaxis), and assist in the timely containment of the outbreak.