In vivo virology core

体内病毒学核心

基本信息

项目摘要

CORE 7: IN VIVO VIROLOGY SUMMARY SARS-CoV-2 continues to cause severe morbidity and mortality in the current pandemic, and future RNA virus epidemics or pandemics are inevitable. To improve patient mortality rates, the development of antiviral therapeutics is critical. However, currently available SARS-CoV-2 antiviral treatments are limited in efficacy. Furthermore, it is imperative that we have access to an arsenal of compounds against all RNA viruses of pandemic potential ready to be deployed into clinical trials at the earliest stages of future pandemics to save millions of lives and reduce long-term disabilities associated with disease. The goal of the QCRG Pandemic Response Program is the identification and development of oral drug candidates with suitable safety profiles for broad use in the outpatient setting. The In Vivo Virology Core plays an essential role in the QCRG Drug Discovery Platform in the Hit-to-Lead and Lead Optimization stages, working closely with Projects 1-6 and the In Vitro Virology and Medicinal Chemistry Cores. Our goal is to determine the therapeutic efficacy of antiviral hits and leads against coronaviruses, flaviviruses, togaviruses, picornaviruses and Bunyavirales in advanced animal models of viral infection. We have assembled a team of investigators with decades of experience in advanced animal models for the analysis of antiviral countermeasures against the target viral families. We will first analyze hit compounds in animal models using single concentration prophylactic treatment of maximal tolerated dose. Compounds that show antiviral activity against viruses in vitro (established by the In Vitro Virology core) and have a favorable PK and toxicity profile in vivo (Medicinal Chemistry Core), will be tested for their ability to inhibit viral replication and disease in mice challenged with coronaviruses, flaviviruses, enteroviruses, togaviruses, and bunyaviruses. For compounds with antiviral activity in vivo in single-dose treatments, we will determine dose responses, time of administration post-challenge for therapeutic activity, and spectrum of activity against multiple strains and viruses (Aim 1). We expect to identify 8-12 or 8-10 Lead Compounds for coronaviruses and other pandemic- potential RNA viruses, respectively. Next, in Aim 2, we will determine antiviral resistance patterns and fitness of resistant mutantsIn addition, beneficial compound combinations identified in vitro (In Vitro Virology Core), will be tested in drug combinations studies in the appropriate animal model, both with known virus inhibitors and with each other. We anticipate being a key component for antiviral development and expect to iterate with Projects and Cores to obtain 3-6 Optimized Leads that will be transferred to our industry partner Roche for clinical development.
核心7:体内病毒学

项目成果

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Adolfo Garcia-Sastre其他文献

Adolfo Garcia-Sastre的其他文献

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{{ truncateString('Adolfo Garcia-Sastre', 18)}}的其他基金

A deep longitudinal analysis of next generation influenza vaccines in older adults
对老年人使用下一代流感疫苗的深入纵向分析
  • 批准号:
    10544172
  • 财政年份:
    2022
  • 资助金额:
    $ 376.07万
  • 项目类别:
Immune phenotyping of responses to influenza virus vaccination and infection
流感病毒疫苗接种和感染反应的免疫表型
  • 批准号:
    10595642
  • 财政年份:
    2022
  • 资助金额:
    $ 376.07万
  • 项目类别:
Admin-Core-001
管理核心-001
  • 批准号:
    10710092
  • 财政年份:
    2022
  • 资助金额:
    $ 376.07万
  • 项目类别:
A deep longitudinal analysis of next generation influenza vaccines in older adults
对老年人使用下一代流感疫苗的深入纵向分析
  • 批准号:
    10342393
  • 财政年份:
    2022
  • 资助金额:
    $ 376.07万
  • 项目类别:
Immune phenotyping of responses to influenza virus vaccination and infection
流感病毒疫苗接种和感染反应的免疫表型
  • 批准号:
    10435237
  • 财政年份:
    2022
  • 资助金额:
    $ 376.07万
  • 项目类别:
Development of CoV inhibitors against non-enzymatic targets
针对非酶靶标的 CoV 抑制剂的开发
  • 批准号:
    10514327
  • 财政年份:
    2022
  • 资助金额:
    $ 376.07万
  • 项目类别:
Vulnerability of SARS- CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses
基于血清学抗体分析的 SARS-CoV-2 感染对肺癌的脆弱性
  • 批准号:
    10222305
  • 财政年份:
    2020
  • 资助金额:
    $ 376.07万
  • 项目类别:
Vulnerability of SARS- CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses
基于血清学抗体分析的 SARS-CoV-2 感染对肺癌的脆弱性
  • 批准号:
    10706729
  • 财政年份:
    2020
  • 资助金额:
    $ 376.07万
  • 项目类别:
Vulnerability of SARS- CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses
基于血清学抗体分析的 SARS-CoV-2 感染对肺癌的脆弱性
  • 批准号:
    10688370
  • 财政年份:
    2020
  • 资助金额:
    $ 376.07万
  • 项目类别:
Core G - IOF Management Core
核心G-IOF管理核心
  • 批准号:
    10153663
  • 财政年份:
    2020
  • 资助金额:
    $ 376.07万
  • 项目类别:

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