Antiviral Drugs for Arenaviruses

沙粒病毒的抗病毒药物

• 批准号: 8076702
• 负责人: SEAN M AMBERG
• 金额: $ 177.92万
• 依托单位: SIGA TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-17 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8076702
• 关键词: Animal Model; Animals; Antiviral Agents; Arenavirus; Binding; Biological; Biological Availability; Categories; Cavia; Chemicals; Chemistry; Clinical; Data; Development; Dose; Drug Interactions; Drug Kinetics; Drug resistance; Evaluation; Foundations; Genetic; Genetic Determinism; Glycoproteins; Goals; Human; In Vitro; Investigational New Drug Application; Junin virus; Lassa Fever; Lassa virus; Lead; Libraries; Macaca fascicularis; Metabolism; Modeling; Monitor; Mutation; Organ; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacology; Pharmacology and Toxicology; Predisposition; Preparation; Proteins; Reporting; Resistance; Ribavirin; Safety; Screening procedure; Series; Solubility; Specificity; Structure; Structure-Activity Relationship; Tacaribe Complex Viruses; Testing; Toxic effect; Toxicology; Variant; Viral; Viral Hemorrhagic Fevers; Virus; analog; analytical method; animal efficacy; base; chemical synthesis; cost effective; drug metabolism; drug resistant virus; efficacy evaluation; fitness; genotoxicity; hemorrhagic fever virus; in vivo; inhibitor/antagonist; large scale production; nonhuman primate; pharmacophore; pre-clinical; prevent; programs; protective efficacy; small molecule

DESCRIPTION (provided by applicant): The goal of the program described here is to develop an antiviral drug for treating and preventing Lassa fever and other hemorrhagic fevers of arenavirus origin. Previous library screening identified several good candidate small molecule inhibitors of Lassa virus entry. Subsequent in vitro and in vivo characterization identified a potent series, ST-193, with broad- spectrum activity against 5 distinct Category A hemorrhagic fever Arenaviruses. This series has shown protective efficacy in two animal models of Lassa fever, guinea pigs and cynomolgus monkeys. The specific objective of this application is to optimize this chemical series to identify an appropriate candidate for preclinical development and to collect the necessary data to support the submission of an application for an Investigational New Drug (IND).

描述（由申请人提供）：本文所述项目的目标是开发一种抗病毒药物，用于治疗和预防拉沙热和其他沙粒病毒来源的出血热。先前的文库筛选鉴定了拉沙病毒进入的几种良好的候选小分子抑制剂。随后的体外和体内表征鉴定了一个有效的系列，ST-193，对5种不同的A类出血热沙粒病毒具有广谱活性。该系列产品已在两种拉沙热动物模型（豚鼠和食蟹猴）中显示出保护功效。本申请的具体目的是优化该化学品系列，以确定临床前开发的适当候选药物，并收集必要的数据以支持提交研究性新药（IND）申请。