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
- 批准号:10448062
- 负责人:
- 金额:$ 24.77万
- 依托单位:
- 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:2022-01-27 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:2019-nCoVAIDS/HIV problemAcquired Immunodeficiency SyndromeAddressAffectAgeAgingAmericanAntibioticsAntiviral AgentsAntiviral TherapyAppearanceBiochemicalBiological AssayBiologyCOVID-19COVID-19 impactCOVID-19 patientCOVID-19 treatmentCOVID-19 vaccinationCOVID-19 vaccineCardiacCardiac developmentCell Culture TechniquesCellsChemicalsChronicClinical TrialsCommunitiesCosts and BenefitsDNADNA DamageDNA Mutational AnalysisDNA Sequence AlterationDNA analysisDNA biosynthesisDeveloping CountriesEchocardiographyEmergency SituationEnzymesEpidemicEvaluationExposure toFDA approvedFunctional disorderFutureGenerationsGenetic TranscriptionHealthHepatitis CHistopathologyHospitalizationIn SituIndividualInfectionInfection ControlIonophoresLasersLeadMediationMedicalMicroscopyMitochondriaMitochondrial DNAMyopathyNatureNucleosidesNucleotidesOutcomeOxidative PhosphorylationPatientsPharmaceutical PreparationsPharmacotherapyPhase II/III Clinical TrialPhysiciansPhysiologyPositioning AttributePre-Clinical ModelPreclinical TestingProteinsRNA replicationReportingResearchResearch PersonnelResistanceRespiratory DiseaseRibonucleosidesRiskRodentRodent ModelSARS-CoV-2 antibodySARS-CoV-2 antiviralSARS-CoV-2 infectionSafetySeverity of illnessSex DifferencesTestingTimeTissuesToxic effectToxicologyVaccinationVaccinesVariantViralViral Load resultVirus DiseasesVirus ReplicationWorkZidovudineage differenceage groupagedanalogantiviral nucleoside analogcombatcoronavirus diseasecoronavirus treatmentexposed human populationin vivoinfection ratemature animalmitochondrial DNA mutationmitochondrial dysfunctionmortalitynegative affectnext generation sequencingnovelnucleoside analogpandemic diseaseparticlepatient populationpre-clinicalprematurepreventremdesivirscreeningsexside effecttreatment responsevaccine hesitancyviral RNAyoung adult
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.
项目总结
项目成果
期刊论文数量(0)
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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:














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