Discovery of novel broad-spectrum coronavirus inhibitors

新型广谱冠状病毒抑制剂的发现

基本信息

批准号：
10845862
负责人：
VINEET D MENACHERY
金额：
$ 79.83万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
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：
2022-05-16 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10845862
关键词：
2019-nCoV Achievement Active Immunization Address Animal Model Animals Antiviral Agents Biochemical Biological Biological Assay Biology Biophysics COVID-19 vaccine Cells Chemicals Civilization Clinical Trials Coronavirus Dengue Virus Development Disease Disease Outbreaks Engineering Epidemic Exclusion Family Flavivirus Future Goals Hamsters Henipavirus Human Humanities In Vitro Infection Interruption Lead Libraries Life Life Cycle Stages Medicine Middle East Respiratory Syndrome Coronavirus Modeling Morbidity - disease rate Mus Mutation Oral Outcome Passive Immunization Peptide Hydrolases Pharmaceutical Chemistry Polymerase Predisposition Process Property Proteins Recombinant Proteins Recombinants Recording of previous events Recurrence Reporter Resistance SARS coronavirus Structure System Testing Therapeutic Toxicology Triage Viral Viremia Virus Virus Inhibitors Virus Replication Work airway epithelium biosafety level 2 facility coronavirus antiviral coronavirus therapeutics drug candidate experience fitness human coronavirus human disease in vivo in vivo Model inhibitor intravenous injection mortality mutant novel novel therapeutics pandemic preparedness pathogen population health preclinical development prevent remdesivir resistance mutation screening small molecule therapeutic target tool

项目摘要

PROJECT 2 – ABSTRACT The goal of this project is to discover novel broad-spectrum coronavirus inhibitors. We will identify new broad- spectrum coronavirus inhibitors of viral replication using a cell-based approach. We will achieve the goal by pursuing three aims. (i) Screen and identify novel compounds for broad-spectrum coronavirus inhibition. We will screen and identify inhibitors of viral replication using SARS-CoV-2, MERS-CoV, and 229E infection assays. UTMB has developed an single-cycle infection system for SARS-CoV-2 that can be used for HTS campaign at BSL2. In this application, we will expand this system to MERS-CoV. We will also develop a reporter 229E coronavirus for antiviral screen. (ii) Develop tool compounds, determine target protein, and optimize molecules. (iii) Evaluate lead compounds in relevant in vitro and in vivo models and select Development Candidate for IND- enabling studies. The proposed cell-based approach may discover novel antiviral targets that may not be tractable for target-based antiviral approach.

项目 2 – 摘要该项目的目标是发现新型广谱冠状病毒抑制剂。使用基于细胞的方法开发新型冠状病毒病毒复制抑制剂，我们将通过以下方式实现这一目标。追求三个目标：（i）筛选和鉴定用于广谱冠状病毒抑制的新化合物。使用 SARS-CoV-2、MERS-CoV 和 229E 感染检测筛选和识别病毒复制抑制剂。 UTMB 开发了一种针对 SARS-CoV-2 的单周期感染系统，可用于 HTS 活动 BSL2。在此应用中，我们将将该系统扩展到 MERS-CoV，我们还将开发报告基因 229E。用于抗病毒筛选的冠状病毒。 (ii) 开发工具化合物、确定目标蛋白并优化分子。 (iii) 评估相关体外和体内模型中的先导化合物，并选择 IND 的开发候选药物所提出的基于细胞的方法可能会发现新的抗病毒靶点，而这些靶点可能不是。易于处理基于目标的抗病毒方法。