grant

Coronavirus Genome Replication

Organization UNIV OF NORTH CAROLINA CHAPEL HILLLocation CHAPEL HILL, UNITED STATESPosted 15 Mar 2021Deadline 28 Feb 2027
NIHUS FederalResearch GrantFY20262019 novel corona virus2019 novel coronavirus2019-nCoV5'-3'-exoribonuclease5'-exoribonucleaseAbscissionAddressBacteriophagesBiochemicalCOVID-19 virusCOVID19 virusCell BodyCellsClinicalCoV emergenceCoV-2CoV2ComplexCore AssemblyCoronaviridaeCoronavirusDNADNA mutationDataDeoxyribonucleic AcidDevelopmentDiseaseDisease OutbreaksDisorderDissociationDrug PrecursorsDrug resistanceEC 2.7.7.48Enzymatic BiochemistryEnzyme GeneEnzymesEnzymologyEquilibriumEventExcisionExonsExonucleaseExoribonucleasesExtirpationFrequenciesGS-5734Gene TranscriptionGeneticGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationGenetic studyGenomeInfection preventionInterventionKineticsKnowledgeLaboratoriesLengthLocationMERS corona virusMERS coronavirusMERS virusMERS-CoVMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMeasuresMiddle East Respiratory Syndrome Corona VirusMiddle East Respiratory Syndrome CoronavirusMiddle East Respiratory Syndrome VirusMiddle East Respiratory Syndrome-CoVMiddle East Respiratory VirusMiddle East Respiratory coronavirusMiddle Eastern Respiratory Syndrome Corona virusMiddle Eastern Respiratory Syndrome CoronavirusMiddle Eastern Respiratory Syndrome VirusMiddle Eastern Respiratory Syndrome-CoVMorbidityMultienzyme ComplexesMutationNon-Polyadenylated RNANon-structural ProteinNonstructural ProteinNucleotidesOrthocoronavirinaeOutbreaksPathway interactionsPhagesPopulationPrevent infectionPro-DrugsProdrugsProkaryotaeProkaryotic CellsProteinsProteomeRNARNA ExpressionRNA Gene ProductsRNA HelicaseRNA ReplicaseRNA VirusesRNA-Dependent RNA PolymeraseRNA-Directed RNA PolymeraseRemovalResearchResistanceRibonucleic AcidRibonucleoside PhosphatesRibonucleotidesRoleSARSSARS VirusSARS corona virusSARS corona virus 2SARS coronavirusSARS coronavirus diseaseSARS-Associated CoronavirusSARS-CO-V2SARS-COVID-2SARS-CoVSARS-CoV diseaseSARS-CoV-1SARS-CoV-2SARS-CoV2SARS-Related CoronavirusSARS-associated corona virus 2SARS-associated coronavirus 2SARS-coronavirus-2SARS-related corona virus 2SARS-related coronavirus 2SARSCoV2ScourgeSevere Acute Respiratory CoronavirusSevere Acute Respiratory Coronavirus 2Severe Acute Respiratory Distress Syndrome CoV 2Severe Acute Respiratory Distress Syndrome Corona Virus 2Severe Acute Respiratory Distress Syndrome Coronavirus 2Severe Acute Respiratory SyndromeSevere Acute Respiratory Syndrome CoV 2Severe Acute Respiratory Syndrome CoV diseaseSevere Acute Respiratory Syndrome VirusSevere Acute Respiratory Syndrome corona virusSevere Acute Respiratory Syndrome coronavirusSevere Acute Respiratory Syndrome coronavirus diseaseSevere Acute Respiratory Syndrome-associated coronavirus 2Severe Acute Respiratory Syndrome-related coronavirus 2Severe acute respiratory syndrome associated corona virus 2Severe acute respiratory syndrome coronavirus 2Severe acute respiratory syndrome related corona virus 2SiteSpecificityStructureSubstrate SpecificitySurgical RemovalSyndromeSystemTherapeuticTranscriptionVekluryViralViral GenomeVirusWuhan coronavirusanti-viral developmentanti-viral drug developmentanti-viral efficacyanti-viral therapeutic developmentanti-viral therapy developmentantiviral developmentantiviral drug developmentantiviral therapeutic developmentantiviral therapy developmentbacterial virusbalancebalance functioncorona viruscorona virus emergencecoronavirus disease 2019 viruscoronavirus disease-19 viruscoronavirus emergencecrosslinkdeveloping anti-viral agentdeveloping anti-viral drugdeveloping anti-viral therapeuticdeveloping anti-viral therapydeveloping antiviral agentdeveloping antiviral drugdeveloping antiviral therapeuticdeveloping antiviral therapydevelopmentaldrug actiondrug resistantemergent CoVemergent corona virusemergent coronavirusemergent pandemicemerging CoVemerging corona virusemerging coronavirusemerging pandemicenzyme complexgenome mutationhCoV19inhibitorinsightmortalitynCoVnCoV2new CoVnew corona virusnew coronavirusnew pandemicnovel CoVnovel corona virusnovel coronavirusnovel pandemicnucleotide analogpandemicpandemic diseasepast outbreakpathwayprevious outbreakprior outbreakprokaryoteremdesivirreplicaseresectionresistance to Drugresistantresistant to Drugsevere acute respiratory syndrome-CoVsingle moleculesocial rolestoichiometrystructural biologytriphosphatetripolyphosphateviral RNAvirus RNAvirus genome
Sign up free to applyApply link · pipeline · email alerts
— or —

Get email alerts for similar roles

Weekly digest · no password needed · unsubscribe any time

Full Description

The world witnessed a global pandemic caused by a second severe acute respiratory syndrome coronavirus (SARS2). In spite of the foreshadowing of such a pandemic by the emergence of SARS1 in 2002 and Middle East respiratory syndrome coronavirus (MERS) in 2012, we were ill equipped to address this scourge. Each of these early outbreaks yielded a substantial body of knowledge on the structures of coronavirus proteins. As with previous outbreaks, we are witnessing a redoubled coronavirus research effort.

Structural biology continues to lead the way; however, our laboratory is now pledging a sustained commitment to elucidation of the fundamental enzymology and corresponding mechanisms of coronavirus genome replication. The SARS2 replisome has emerged as a clinically tractable target for development antiviral therapeutics. Remdesivir is a nucleotide analog prodrug, metabolized to the triphosphate in cells, and incorporated by the SARS2 replisome without excision by its proofreading exonuclease, ExoN. The mechanism of action of remdesivir is unclear, and the mechanism of escape from ExoN is unknown.

This circumstance reflects the absence of a quantitative, mechanistic perspective of the SARS2 replisome. Such a perspective will be essential to elucidation of the mechanism of drug action and the mechanism of drug resistance. We have demonstrated the feasibility of elucidating the principles governing the dynamics and function of the SARS2 core replicase using state-of-the-art ensemble and single-molecule approaches. We will exploit these advances to pursue the following specific aims: study assembly and function of the SARS2 core replicase and its sub-assemblies (Aim 1); study utilization of incorrect nucleotides and nucleotide analogues by the SARS2 core replicase (Aim 2); and study the mechanism of error correction by the SARS2 exoribonuclease (Aim 3).

Completion of these studies will represent the first, deep dive into the mechanistic enzymology of the coronavirus replisome.

Grant Number: 5R01AI161841-05
NIH Institute/Center: NIH
Principal Investigator: CRAIG CAMERON

Sign up free to get the apply link, save to pipeline, and set email alerts.

Sign up free →

Agency Plan

7-day free trial

Unlock procurement & grants

Upgrade to access active tenders from World Bank, UNDP, ADB and more — with email alerts and pipeline tracking.

$29.99 / month

  • 🔔Email alerts for new matching tenders
  • 🗂️Track tenders in your pipeline
  • 💰Filter by contract value
  • 📥Export results to CSV
  • 📌Save searches with one click
Start 7-day free trial →

Explore more

📍 More grants in UNITED STATES🏷 More NIH opportunities🏷 More US Federal opportunities🏷 More Research Grant opportunities🏢 All nih_reporter opportunities