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（由调查人员提供）：9月11日的恐怖事件和最近的犯罪炭疽病暴露在于人们对使用天花作为生物武器的意识提高了人们的意识。疫苗短缺和与疫苗相关死亡的发生率将排除每个人，特别是免疫功能低下的患者。目前，没有FDA批准的天花治疗药物。最近的文献表明，利福平，西多福韦和维拉唑（利巴韦林）对天花有效。但是，所有人都有后勤和医疗并发症，这些并发症排除了它们的有效使用。因此，将需要更有效，更安全的药物来对抗暴露的人。 由于微环境的多样化，海洋和海洋包含大量的微生物，这些微生物在遗传上与其陆地对应物不同，并且代表了隔离独特的反病毒疗法的新途径。该阶段I应用的总体目标是鉴定和纯化对抗谷菌病毒（VV）生物活性的海洋微生物的化合物。在第二阶段，我们将使用纯化化合物进行体外研究，包括对作用机理的详细评估。第二阶段的目标是具有与FDA一起使用IND提交的VV的独特化合物，进行了必要的体内临床试验，并启动抗SmallPox Therapeatics作为III期商业化工作中的抗SmallPox Therapeatics作为一种先发制的抗亲生恐怖措施。 关键词：天花，生物恐怖，治疗剂，疫苗，抗病毒药，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Smallpox药物将对美国的生物安全有很大的好处。这种药物在商业上也可能对其他自然和新兴的病毒威胁变得很重要。