Evidence map›Paper›PMID 40483926›Full record

ArticleBioorganic & medicinal chemistry2025

Exploration of 4'-fluoro fleximer nucleoside analogues as potential broad-spectrum antiviral agents.

Kyle A Davis, Jason K Smith, Jessica L Smith, Meareg Amare, Meghan V Diefenbacher, Peter Halfmann, Timothy P Sheahan, Alec J Hirsch, Katherine L Seley-Radtke

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Kyle A DavisDepartment of Chemistry & Biochemistry, University of Maryland, Baltimore County, Baltimore, MD, USA.
Jason K SmithDepartment of Chemistry & Biochemistry, University of Maryland, Baltimore County, Baltimore, MD, USA.
Jessica L SmithVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA.
Meareg AmareInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Meghan V DiefenbacherDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Peter HalfmannInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Timothy P SheahanDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alec J HirschVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA.
Katherine L Seley-RadtkeDepartment of Chemistry & Biochemistry, University of Maryland, Baltimore County, Baltimore, MD, USA. Electronic address: kseley@umbc.edu.

Funding

Research Project 1: Coronavirus antiviral lead development and combination testingU19AI171292 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S · 2022 to 2022
$65.5M
Graduate Training at The Chemistry Biology InterfaceT32GM066706 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE COUNTY · PI SELEY-RADTKE, KATHERINE L, SMITH, AARON T · 2004 to 2023
$3.3M
Graduate Training at The Chemistry Biology InterfaceT32GM158458 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE COUNTY · PI Steven Fletcher, Aaron T Smith · 2025 to 2026
$564k
NIAID NIH HHS U19 AI171292NIGMS NIH HHS T32 GM066706NIGMS NIH HHS T32 GM158458
6 · The paper itself

Abstract

A series of 4'-fluoro fleximer nucleoside analogues in addition to their corresponding prodrugs were designed, synthesized, and evaluated for their antiviral potential. The impetus for this series was based on the success of other 4'-modified nucleoside antiviral drugs such as adafosbuvir and balapiravir. One analogue, KAD-008, exhibited potent, low single-digit micromolar activity against DENV-2. Another analogue, KAD-025, had broad-spectrum antiviral activity across several viral families including flaviviruses, filoviruses, and coronaviruses. All of the analogues tested showed no toxicity up to 100 µM. Additional studies are underway to elucidate the mechanism of action for these compounds and to synthesize additional 4'-modified fleximer nucleoside analogues with different 4'-modifications to compare their antiviral activities.

Indexed as

Antiviral AgentsNucleosidesAnimalsDengue VirusDose-Response Relationship, DrugFlavivirusHumansMicrobial Sensitivity TestsMolecular StructureStructure-Activity RelationshipAntiviral AgentsNucleosidesAntiviralDengueFleximersNucleosidesProdrugs

Identifiers

PMID40483926
PMCPMC12276918

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.