Antiviral Drugs for Category A Arenavirus

描述（由申请人提供）：生物恐怖主义威胁最高的病原体，A类制剂，如果以恶意方式使用，最有可能造成不利的公共卫生影响和大规模伤亡。在A类病毒中，有五种出血热沙粒病毒（拉沙病毒、朱宁病毒、马丘波病毒、瓜纳里托病毒和萨比亚病毒）。目前，没有特定的抗病毒治疗批准用于对抗沙粒病毒出血热。我们的沙粒病毒抗病毒项目的总体目标是通过FDA批准推进至少一种小分子抗病毒药物，用于治疗和预防由A类沙粒病毒引起的病毒性出血热，该药物将安全，有效，并以胶囊，片剂或液体口服给药，用于治疗，暴露后预防和预防应用。该SBIR II期沙粒病毒项目的目标是将我们在SBIR I期工作中发现的早期沙粒病毒特异性抗病毒化合物推进到化学优化中，通过动物疗效，IND使能毒理学和其他临床前活动，进入我们将提交IND申请的临床开发阶段候选药物。人体安全性和药代动力学研究超出了II期工作计划的范围。在这项为期3年的SBIR II期沙粒病毒项目结束时，我们预计将提交至少一份用于治疗和预防A类沙粒病毒感染的抗病毒候选药物IND申请，并确定至少一种额外的沙粒病毒临床前候选药物。沙粒病毒特异性抗病毒药物的可用性将通过在潜在的生物恐怖袭击中对A类沙粒病毒的使用起到重要的威慑和防御作用来满足国家和全球安全需求。抗病毒药物可以随时储存，并在沙粒病毒爆发时迅速部署。由于抗病毒药物易于服用（口服药丸或液体），并迅速发挥其抗病毒作用（在服用后数小时内），它们将有助于有效治疗患病患者，保护那些怀疑接触病原体的人（接触后预防），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.