Anti-Smallpox Therapeutics from Marine Micoorganisms

海洋微生物的抗天花疗法

• 批准号: 6691390
• 负责人: TREVOR P. CASTOR
• 金额: $ 26.47万
• 依托单位: APHIOS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6691390
• 关键词: Poxviridae disease; animal extract; antiviral agents; aquatic organism; bioassay; biological products; biotechnology; bioterrorism /chemical warfare; cytoprotection; drug discovery /isolation; drug screening /evaluation; high performance liquid chromatography; mass spectrometry; microorganism; nuclear magnetic resonance spectroscopy; plant extracts; polymerase chain reaction; restriction fragment length polymorphism; saltwater environment; smallpox virus; vaccine evaluation; vaccinia virus

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.

描述（由调查员提供）：9 月 11 日的恐怖事件和最近发生的炭疽犯罪事件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将妨碍对每个人，特别是免疫功能低下患者的保护。目前，FDA 还没有批准治疗天花的药物。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，所有这些都存在后勤和医疗方面的并发症，妨碍了它们的有效使用。因此，需要更有效、更安全的药物来对抗接触天花的人。 由于微环境的多样性，海洋含有丰富的微生物，这些微生物在基因上与陆地微生物不同，代表了分离独特抗病毒疗法的新途径。第一阶段应用的总体目标是识别和纯化来自海洋微生物的具有抗痘苗病毒（VV）生物活性的化合物。在第二阶段，我们将使用纯化的化合物进行体外研究，包括对作用机制的详细评估。第二阶段的目标是拥有一种有效对抗 VV 的独特化合物，准备向 FDA 提交 IND，进行必要的体内临床试验，并启动抗天花治疗药物的储备，作为第二阶段的先发制人的反恐措施三、商业化努力。 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为美国的生物安全带来巨大利益。此类药物对于对抗其他自然和新出现的病毒威胁也可能变得具有商业重要性。