Anti-Smallpox Therapeutics from Marine Micoorganisms

描述(由调查人员提供)：9.11恐怖事件和最近的犯罪炭疽热暴露提高了人们对使用天花作为生物武器的认识。疫苗短缺和疫苗相关死亡的发生率将排除对每个人，特别是免疫受损患者的保护。目前，还没有FDA批准的治疗天花的药物。最近的文献表明，利福平、西多福韦和病毒唑(利巴韦林)对天花有效；然而，它们都有后勤和医疗并发症，阻碍了它们的有效使用。因此，将需要更有效和更安全的药物来对抗那些接触天花的人。 由于微环境的多样性，海洋中含有丰富的微生物，这些微生物在基因上与陆地上的微生物不同，是分离独特的抗病毒疗法的新途径。这一第一阶段应用的总体目标是从海洋微生物中鉴定和纯化对痘苗病毒(VV)具有生物活性的化合物。在第二阶段，我们将对纯化的化合物进行体外研究，包括详细的作用机制评估。第二阶段的目标是有一种独特的有效对抗VV的化合物准备好向FDA提交IND，进行必要的体内临床试验，并开始储备抗天花治疗药物，作为第三阶段商业化努力中的先发制人的反生物恐怖主义措施。 关键词：天花，生物恐怖主义，治疗学，牛痘，抗病毒药物，海洋微生物。 潜在的商业应用：从易于发酵的海洋微生物资源中开发独特且具有成本效益的抗天花药物将对美国的生物安全产生巨大的好处。针对其他自然和新出现的病毒威胁，这类药物也可能在商业上变得重要。

DESCRIPTION (provided by investigator): The terrorist events of September 11th and the recent criminal anthrax exposures have increased awareness of the use of smallpox as a biological weapon. A shortage of the vaccine and the incidence of vaccine-related deaths will preclude protection of everyone especially immunocompromised patients. Currently, there are no FDA approved drugs for the treatment of smallpox. Recent literature has suggested that rifampicin, cidofovir, and virazole (ribavirin) are effective against smallpox; all, however, have logistical and medical complications that preclude their effective use. Thus, more effective and safer drugs will be required to combat smallpox in those exposed. Due to diverse microenvironments, oceans and seas contain a wealth of microorganisms that are genetically different from their terrestrial counterparts and represent a new avenue for isolating unique anti-viral therapeutics. The overall goal of this Phase I application is to identify and purify compounds from marine microorganisms that are bioactive against Vaccinia virus (VV). In Phase II, we will conduct in vitro studies with the purified compound, including a detailed evaluation of mechanisms of action. The goal for Phase II is to have a unique compound effective against VV ready for filing with an IND with the FDA, conducting the necessary in vivo clinical trials and initiating the stockpiling of anti-smallpox therapeutics as a preemptive anti-bioterrorism measure in a Phase III commercialization effort. Keywords: Smallpox, Bioterrorism, Therapeutics, Vaccinia, Antiviral Drugs, Marine Microorganisms. Potential Commercial application: The development of unique and cost-effective anti-smallpox drugs from a readily fermentable marine microorganism resource will be of tremendous benefit to the biosecurity of the United States. Such drugs may also become commercially important against other natural and emerging viral threats.