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Optimizing Ridaifen-B analogs as potential therapeutics for Ebola viruses

优化 Ridaifen-B 类似物作为埃博拉病毒的潜在疗法

基本信息

批准号：
10586633
负责人：
Lijun Rong
金额：
$ 79.52万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-20 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10586633
关键词：
Animal Model Antiviral Therapy Binding Biological Assay Bundibugyo virus Characteristics Chemicals Clinic Complex Democratic Republic of the Congo Dose Drug Kinetics Ebola Ebola Hemorrhagic Fever Ebola virus Estrogen Receptors Exhibits GP2 gene GTPBP1 gene Glycoproteins Goals Human In Vitro Incidence Infection Lead Libraries Life Ligands Maximum Tolerated Dose Mediating Medical Mus Pharmaceutical Preparations Prevalence Property Reporting Research Resolution Reston Ebola virus Route Safety Selective Estrogen Receptor Modulators Series Structure Sudan Sudan Ebola virus Tamoxifen Therapeutic Time Toremifene Toxicokinetics Viral Viral Hemorrhagic Fevers Viral Pathogenesis Virus Virus Diseases Work Zoonoses analog antiviral drug development base cost efficacy evaluation forest guinea pig model in vivo evaluation inhibitor lead optimization mortality nonhuman primate novel pre-clinical prophylactic remote location scaffold scale up side effect small molecule small molecule inhibitor small molecule libraries therapeutic candidate therapeutic target therapeutically effective

项目摘要

Summary Ebola virus disease (EVD) is caused by an infection with a group of viruses within the genus Ebolavirus. There are at least five species of Ebolavirus, Ebola virus (Zaire, EBOV), Ebola Sudan (SUDV), Bundibugyo virus (BDBV), Reston virus and Tai Forest virus (TAFV). Infections with these viruses can cause severe hemorrhagic fevers in humans and nonhuman primates, and are associated with up to 90% mortality rates with EBOV. Because of the safety concerns, these viruses are designated as the biosafety level 4 agents. Currently there is no effective therapeutic treatments against Ebola virus infection and pathogenesis in humans. Thus the goal of this application is to develop GP-specific small molecule inhibitors as drugs which can be used prophylactically and therapeutically against EBOV and other Ebola virus infections. To achieve this, we screened an in-house library of small molecules, and identified numerous potent entry inhibitors against EBOV. We have identified a series of potent compounds and will use them as leads which will be chemically optimized and developed as an anti-Ebola virus therapy candidate. In this application, two specific aims are proposed: (1) structure- based optimization of the lead compounds, and (2) In vivo evaluation of the lead compounds against EBOV infection using animal models.

总结