Advancement of antiviral inhibitors of chikungunya virus

基孔肯雅病毒抗病毒抑制剂的研究进展

• 批准号: 10132230
• 负责人: Daniel C Pevear
• 金额: $ 100万
• 依托单位: VENATORX PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-13 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10132230
• 关键词: Address; Aedes; Alphavirus; Americas; Ames Assay; Antiviral Agents; Arboviruses; Arthralgia; Binding Proteins; Bioavailable; Biological; Biological Availability; Blood Circulation; Canis familiaris; Caribbean region; Category C pathogen; Cell Culture Techniques; Cell Line; Centers for Disease Control and Prevention (U.S.); Chemicals; Chikungunya virus; Culicidae; DNA Viruses; Development; Dose; Drug Evaluation; Drug Kinetics; Epidemic; Europe; Exposure to; Fever; Florida; Goals; Health; Human; In Vitro; Individual; Infection; Lead; Libraries; Liver Microsomes; Modeling; Molecular Target; Morbidity - disease rate; Mus; Musculoskeletal Pain; Mutagenicity Tests; National Institute of Allergy and Infectious Disease; Oral; Pathogenicity; Permeability; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacology Study; Phase; Polyarthralgias; Population; Positioning Attribute; Prevention; Property; Protein Isoforms; RNA; Rattus; Reporting; Risk; Safety; Series; Serum Proteins; Signal Transduction; Small Business Innovation Research Grant; Solubility; Structure-Activity Relationship; Texas; Time; Toxic effect; Toxicology; Vaccines; Virus; Virus Inhibitors; Virus Replication; acute toxicity; candidate selection; chikungunya infection; cytotoxic; experience; genotoxicity; improved; in vivo; inhibitor/antagonist; lead optimization; lead series; novel therapeutics; pathogen; safety study; scale up; screening; transmission process; vector mosquito

PROJECT SUMMARY Novel therapies for the treatment of chikungunya virus (CHIKV) infections are urgently needed to address the alarming spread of this pathogen across the Americas. We have identified three distinct series of potent, selective, and orally bioavailable inhibitors of CHIKV replication. In this Phase II renewal SBIR project, we will optimize these series of CHIKV inhibitors to Pre-Development stage and advance a first ever CHIKV antiviral candidate to IND-enabling studies. To accomplish this task, we will execute an integrated medicinal chemistry optimization/biological profiling campaign to optimize the potency, drug-like properties and oral exposure of each series. One or more Pre-Development Candidates will be identified and advanced through candidate selection studies into non-GLP repeat-dose tox in both rats and dogs.

项目摘要 迫切需要用于治疗基孔肯雅病毒（CHIKV）感染的新疗法来解决这些问题。 这种病原体在美洲的惊人传播我们已经确定了三个不同的系列， 选择性和口服生物可利用的CHIKV复制抑制剂。在第二阶段更新SBIR项目中，我们将 将这些系列的CHIKV抑制剂优化到预开发阶段，并推进有史以来第一个CHIKV抗病毒药物 候选人为IND赋能研究。为了完成这项任务，我们将执行一个综合的药物化学 优化/生物特征分析活动，以优化每种药物的效价、药物样性质和口服暴露 系列.一个或多个预开发候选人将通过候选人选择确定和推进 大鼠和犬的非GLP重复给药毒性研究。