Novel Orthopox Small Molecule Anti-Virals

新型 Orthopox 小分子抗病毒药物

• 批准号: 6886133
• 负责人: MURTY N ARIMILLI
• 金额: $ 31.34万
• 依托单位: TRANSTECH PHARMA, LLC
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-15 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6886133
• 关键词: CHO cells; Poxviridae; antiviral agents; binding sites; bioterrorism /chemical warfare; dogs; drug design /synthesis /production; drug screening /evaluation; laboratory rat; microsomes; pharmacokinetics; protease inhibitor; small molecule; smallpox virus; tissue /cell culture; vaccinia virus

DESCRIPTION (provided by applicant): The identification of agents that can either treat or halt the spread of smallpox or other diseases caused by orthopox viruses would have great benefit in mitigating the risk of the orthopox virus being used as a biological weapon. Furthermore such agents would be useful as a therapeutic for accidental exposure to other orthopox viruses such as the recently publicized cases of monkey pox caused by human exposure to exotic imported animals. The ideal therapeutic would be an effective and safe orally available small molecule that could be taken by individuals who were exposed to an orthopox virus or had active disease. Recent evidence suggests that the proteolytic activity of a novel protease encoded by the orthopox virus genome is an obligatory event for viral proliferation. Using a proprietary process of drug discovery called TTP Translational Technology TM that combines novel medicinal chemistry with computer modeling and a series of in vitro biological screening assays, TransTech Pharma proposes to discover small molecule inhibitors of the orthopox protease that have drug like characteristics in terms of potency, safety and pharmacokinetic characteristics as a first step in developing a therapeutic anti-viral for the treatment of infections caused by the orthopox virus.

描述（由申请人提供）：鉴定出能够治疗或阻止天花或由正痘病毒引起的其他疾病传播的药物，对于减轻正痘病毒被用作生物武器的风险将大有裨益。此外，此类试剂可用作意外暴露于其他正痘病毒的治疗剂，例如最近公布的由人类暴露于外来进口动物引起的猴痘病例。理想的治疗方法是一种有效且安全的口服小分子，可供暴露于正痘病毒或患有活动性疾病的个体服用。最近的证据表明，正痘病毒基因组编码的新型蛋白酶的蛋白水解活性是病毒增殖的必然事件。 TransTech Pharma 采用称为 TTP Translational Technology TM 的专有药物发现流程，将新颖的药物化学与计算机建模和一系列体外生物筛选测定相结合，旨在发现 Orthopox 蛋白酶的小分子抑制剂，这些抑制剂在以下方面具有药物样特征：效力、安全性和药代动力学特征是开发用于治疗正痘病毒引起的感染的治疗性抗病毒药物的第一步。