Effects of SARS-CoV-2 Antiviral Ribonucleoside Analogues on Mitochondrial DNA

SARS-CoV-2 抗病毒核糖核苷类似物对线粒体 DNA 的影响

基本信息

项目摘要

PROJECT SUMMARY Antiviral nucleoside analogues are a type of broad-spectrum medication used to prevent viral replication. Only one FDA approved treatment for COVID-19 is a nucleoside analogue and was used under FDA emergency directive to reduce hospitalization times to treat patients infected with the SARS-CoV-2. However, in the past, FDA approved antiviral ribonucleoside analogues used to control infection during the US HIV/AIDS epidemic were shown years later to cause mitochondrial DNA mutations, mitochondrial dysfunction, myopathies, and cause chronic side effects to treated patients. This proposal addresses whether these novel antiviral ribonucleoside analogues (Remdesivir) currently the only FDA approved mediation or (N4-Hydroxycytidine) in Phase II/III clinical trials for COVID-19 affect mitochondrial DNA and mitochondrial function causing cellular and tissue dysfunction. This proposal will use NextGen sequencing, biochemical approaches, mitochondrial assays, and preclinical rodent models of different strains, sexes, and ages to address the following aims. Aim 1: Characterize mtDNA alterations and consequences to OXPHOS function after exposure to a panel of antiviral ribonucleoside analogues. Aim 2: Determine if antiviral ribonucleoside analogues differentially affect mitochondrial function in aged physiology. Even though vaccines are now available for COVID-19, vaccine hesitancy and the appearance of more transmissible SARS-CoV-2 strains are an emerging threat. Also, antiviral nucleoside analogues are often recycled for new viral infections as in the case of Remdesivir which was initially developed against Hepatitis C. This means that these medications may be reused in future viral infections. The research and medical community needs to know whether these antiviral ribonucleoside analogues have off- target side effects, so physicians will be able to make better informed decisions on the costs and benefits of these type of medications for their patients.
项目摘要 抗病毒核苷类似物是一种用于防止病毒复制的广谱药物。只 FDA批准的一种COVID-19治疗药物是核苷类似物,并在FDA紧急情况下使用 该指令旨在减少治疗感染SARS-CoV-2患者的住院时间。然而,在过去, FDA批准用于控制美国艾滋病毒/艾滋病流行期间感染的抗病毒核糖核苷类似物 多年后被证明会导致线粒体DNA突变、线粒体功能障碍、肌病, 对治疗的病人造成慢性副作用。该提案涉及这些新的抗病毒药物是否 核糖核苷类似物(Remdesivir)是目前FDA批准的唯一一种药物, COVID-19的II/III期临床试验影响线粒体DNA和线粒体功能,导致细胞和 组织功能障碍该提案将使用NextGen测序,生物化学方法,线粒体分析, 以及不同品系、性别和年龄的临床前啮齿动物模型,以实现以下目的。目标1: 描述暴露于一组抗病毒药物后mtDNA的改变和对OXPHOS功能的影响 核糖核苷类似物。目的2:确定抗病毒核糖核苷类似物是否差异影响 线粒体在老年生理学中的作用尽管现在已有针对COVID-19的疫苗, 犹豫不决和出现更易传播的SARS-CoV-2病毒株是一个新出现的威胁。此外,抗病毒 核苷类似物经常被回收用于新的病毒感染,如Remdesivir, 是针对丙型肝炎的这意味着这些药物可以在未来的病毒感染中重复使用。的 研究和医学界需要知道这些抗病毒的核糖核苷类似物是否具有关闭, 目标的副作用,因此医生将能够作出更好的知情决定的成本和效益, 这类药物对患者的影响。

项目成果

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Alicia M Pickrell其他文献

Alicia M Pickrell的其他文献

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{{ truncateString('Alicia M Pickrell', 18)}}的其他基金

Effects of SARS-CoV-2 Antiviral Ribonucleoside Analogues on Mitochondrial DNA
SARS-CoV-2 抗病毒核糖核苷类似物对线粒体 DNA 的影响
  • 批准号:
    10557154
  • 财政年份:
    2022
  • 资助金额:
    $ 24.77万
  • 项目类别:
Global Intracellular Responses to Mitophagy
对线粒体自噬的整体细胞内反应
  • 批准号:
    10707665
  • 财政年份:
    2021
  • 资助金额:
    $ 24.77万
  • 项目类别:
Global Intracellular Responses to Mitophagy
对线粒体自噬的整体细胞内反应
  • 批准号:
    10264447
  • 财政年份:
    2021
  • 资助金额:
    $ 24.77万
  • 项目类别:
Global Intracellular Responses to Mitophagy
对线粒体自噬的整体细胞内反应
  • 批准号:
    10469574
  • 财政年份:
    2021
  • 资助金额:
    $ 24.77万
  • 项目类别:
Global Intracellular Responses to Mitophagy
对线粒体自噬的整体细胞内反应
  • 批准号:
    10631204
  • 财政年份:
    2021
  • 资助金额:
    $ 24.77万
  • 项目类别:
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