Taking aim at HBV eradication using novel NRTIs and Capsid effectors
Taking aim at HBV eradication using novel NRTIs and Capsid effectors
批准号:
9918244
负责人:
Stefan G Sarafianos
金额:
$56.87万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-11-01 至 2022-05-31
关键词:
2&apos-deoxyadenosineAcquired Immunodeficiency SyndromeAddressAnti-Retroviral AgentsAntiviral AgentsBiological AssayCapsidCatabolismCell LineCellsChronicCircular DNACirrhosisClinical MarkersCombined Modality TherapyCore ProteinCrystallizationCrystallographyDNADataDeoxyguanosineDevelopmentDrug TargetingFamilyFutureGoalsGroup StructureHIVHIV drug resistanceHepatitis BHepatitis B TherapyHepatitis B VirusHepatitis B e AntigensHepatitis C virusHepatocyteHepatologyHighly Active Antiretroviral TherapyImmunofluorescence ImmunologicIndividualLaboratoriesLeadLife Cycle StagesLinkMaintenanceMalignant neoplasm of liverMethodsMolecularMonitorMulti-Drug ResistanceNuclearNucleocapsidNucleosidesPatientsPharmaceutical PreparationsPolymerasePublicationsPublishingRNAResistanceReverse Transcriptase InhibitorsReverse TranscriptionRoleStructureStructure-Activity RelationshipTimeVaccinesViralViral Load resultViral ProteinsVirusVirus DiseasesVirus ReceptorsVirus ReplicationWestern BlottingWorkanti-hepatitis Bbaseclinical developmentclinically relevantcytotoxicitydeoxyguanosine triphosphatedesigndrug developmententecavirexperiencefight againsthigh riskinhibitor/antagonistinsightmolecular modelingnovelnovel therapeuticsoverexpressionpgRNApolymerizationpreventprotein expressionpublic health relevanceresistant strainresponsesynergismtherapy developmenttreatment responsetripolyphosphateviral DNAviral RNAvirology
中文摘要
点击翻译按钮获取中文摘要
英文摘要
PROJECT SUMMARY
More than 350 million people are chronically infected by Hepatitis B Virus (HBV) and are at high risk for
developing cirrhosis and liver cancer. Current drugs do not cure HBV and do not target covalently closed-
circular DNA (cccDNA), which has been linked to viral persistence in HBV-infected hepatocytes. Moreover,
current therapies require lifetime treatment to suppress viral load and prolonged treatments lead to the
development of drug resistant strains. Finally, there is only a single family of directly acting antiretrovirals
(DAAs) that can block HBV infection, preventing meaningful combination therapies equivalent to formidable
highly active antiretroviral therapies (HAART) that tipped the scales in the fight against AIDS.
The long term goal of this work is to develop HBV therapies that lead to HBV eradication. It is hypothesized
that combinations of novel, potent, and selective inhibitors of HBV can lead to more efficient suppression of
reverse transcription (RT), lack of cross-resistance, synergistic mechanism of action and depletion of cccDNA,
which in turn could lead to the eradication of HBV. Towards that end, this project focuses on the development
of leads that target viral replication by capsid assembly effectors (CAEs) and highly potent novel NRTIs. The
following specific aims are proposed:
Specific Aim 1: Characterize the potency determinants of novel highly active NRTIs.
Specific Aim 2: Discovery and characterization of novel capsid assembly effectors (CAEs)
Specific Aim 3: Characterization of novel NRTI and CAE combinations
These studies will identify promising leads for the development of future anti-HBV drugs from two different
classes and will help design novel combinations that should efficiently suppress cccDNA by targeting Cp and
include highly potent HBV NRTIs towards a sustained virological response that could lead to HBV eradication.
期刊论文(4)
专著(0)
科研奖励(0)
会议论文
DOI:
10.3390/v13050770
发表时间:
2021-04-27
期刊:
Viruses
影响因子:
--
作者:
[Senaweera S, Du H, Zhang H, Kirby KA, Tedbury PR, Xie J, Sarafianos SG, Wang Z]
通讯作者:
Wang Z
Discovery of SARS-CoV-2 antivirals using a replicon assay
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批准号:10522048
-
项目类别:
-
资助金额:$65.76万
-
财政年份:2022
-
负责人:Stefan G Sarafianos
-
依托单位:
Behavior of HIV in Viral Environments (B-HIVE)
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批准号:10650864
-
项目类别:
-
资助金额:$675.93万
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财政年份:2022
-
负责人:Stefan G Sarafianos
-
依托单位:
Discovery of SARS-CoV-2 antivirals using a replicon assay
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批准号:10673119
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项目类别:
-
资助金额:$64.35万
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财政年份:2022
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负责人:Stefan G Sarafianos
-
依托单位:
Dynamics of HIV Core Interactions
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批准号:10650881
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项目类别:
-
资助金额:$117.14万
-
财政年份:2022
-
负责人:Stefan G Sarafianos
-
依托单位:
Behavior of HIV in Viral Environments (B-HIVE)
-
批准号:10508443
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项目类别:
-
资助金额:$628.9万
-
财政年份:2022
-
负责人:Stefan G Sarafianos
-
依托单位:
Dynamics of HIV Core Interactions
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批准号:10508450
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项目类别:
-
资助金额:$122.86万
-
财政年份:2022
-
负责人:Stefan G Sarafianos
-
依托单位:
Ultrapotent Inhibitors of Wild-type and Multi-drug Resistant HIV
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批准号:9605989
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项目类别:
-
资助金额:$27.04万
-
财政年份:2017
-
负责人:Stefan G Sarafianos
-
依托单位:
Taking aim at HBV eradication using novel NRTIs and Capsid effectors
-
批准号:9605893
-
项目类别:
-
资助金额:$42.53万
-
财政年份:2017
-
负责人:Stefan G Sarafianos
-
依托单位:
Reverse Transcriptase Multi-Class Drug Resistance and Rilpivirine Susceptibility in Diverse HIV-1 Subtypes
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批准号:9140626
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项目类别:
-
资助金额:$37.37万
-
财政年份:2016
-
负责人:Stefan G Sarafianos
-
依托单位:
Development of HIV capsid-targeting antivirals that affect immune response by modulating capsid stability and have improved resistance profiles
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批准号:10437037
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项目类别:
-
资助金额:$53.81万
-
财政年份:2016
-
负责人:Stefan G Sarafianos
-
依托单位:
Reverse Transcriptase Multi-Class Drug Resistance and Rilpivirine Susceptibility in Diverse HIV-1 Subtypes
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批准号:9353524
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项目类别:
-
资助金额:$12.41万
-
财政年份:2016
-
负责人:Stefan G Sarafianos
-
依托单位:
Development of HIV capsid-targeting antivirals that affect immune response by modulating capsid stability and have improved resistance profiles
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批准号:10337556
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项目类别:
-
资助金额:$55.14万
-
财政年份:2016
-
负责人:Stefan G Sarafianos
-
依托单位:
Reverse Transcriptase Multi-Class Drug Resistance and Rilpivirine Susceptibility in Diverse HIV-1 Subtypes
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批准号:9280986
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项目类别:
-
资助金额:$7.75万
-
财政年份:2016
-
负责人:Stefan G Sarafianos
-
依托单位:
Development of HIV capsid-targeting antivirals that affect immune response by modulating capsid stability and have improved resistance profiles
-
批准号:10620713
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项目类别:
-
资助金额:$53.44万
-
财政年份:2016
-
负责人:Stefan G Sarafianos
-
依托单位:
Structural studies of HIV Capsid with host factors and Capsid-targeting antivirals
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批准号:8993516
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项目类别:
-
资助金额:$46.59万
-
财政年份:2015
-
负责人:Stefan G Sarafianos
-
依托单位:
Structural studies of HIV Capsid with host factors and Capsid-targeting antivirals
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批准号:9285721
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项目类别:
-
资助金额:$16.05万
-
财政年份:2015
-
负责人:Stefan G Sarafianos
-
依托单位:
Structural studies of HIV Capsid with host factors and Capsid-targeting antivirals
-
批准号:9089958
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项目类别:
-
资助金额:$51.15万
-
财政年份:2015
-
负责人:Stefan G Sarafianos
-
依托单位:
Capsid-Targeting Small Molecules Blocking HIV through Novel Mechanism of Action
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批准号:8802860
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项目类别:
-
资助金额:$22.61万
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财政年份:2014
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负责人:Stefan G Sarafianos
-
依托单位:
Capsid-Targeting Small Molecules Blocking HIV through Novel Mechanism of Action
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批准号:8731597
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项目类别:
-
资助金额:$18.78万
-
财政年份:2014
-
负责人:Stefan G Sarafianos
-
依托单位:
Novel antivirals targeting the RNase H activity of HIV reverse transcriptase
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批准号:9089807
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项目类别:
-
资助金额:$74.94万
-
财政年份:2012
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负责人:Stefan G Sarafianos
-
依托单位:
海外基金