Evidence map›Paper›PMID 40900943›Full record

ArticleNAR molecular medicine2025

Mechanism and spectrum of inhibition of viral polymerases by 2'-deoxy-2'-β-fluoro-4'-azidocytidine or azvudine.

Hery W Lee, Egor P Tchesnokov, Laura J Stevens, Tia M Hughes, Meghan V Diefenbacher, Emma Woolner, Dana Kocincova, David C Schultz, Sara Cherry, Timothy P Sheahan and 2 more

Abstract read
In one paragraph

Article in NAR molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
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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

12 authors.

Hery W LeeDepartment of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada.ORCID https://orcid.org/0000-0002-3981-0284
Egor P TchesnokovDepartment of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada.
Laura J StevensDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
Tia M HughesDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
Meghan V DiefenbacherDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Emma WoolnerDepartment of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada.
Dana KocincovaDepartment of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada.
David C SchultzDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, United States.ORCID https://orcid.org/0000-0002-7890-8815
Sara CherryDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, United States.ORCID https://orcid.org/0000-0003-3956-6610
Timothy P SheahanDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.ORCID https://orcid.org/0000-0001-9181-2183
Mark R DenisonDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, United States.ORCID https://orcid.org/0000-0003-2655-0900
Matthias GötteDepartment of Medical Microbiology & Immunology, University of Alberta, Edmonton, AB T6G 2E1, Canada.ORCID https://orcid.org/0000-0001-6213-5806

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The therapeutic value of antiviral nucleoside analogs was highlighted during the coronavirus disease 2019 (COVID-19) pandemic, with remdesivir and molnupiravir repurposed for their broad-spectrum antiviral activity. The cytidine analog azvudine (FNC) has recently gained attention as a potential treatment for human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Considering the distinct substrate specificities of HIV-1 reverse transcriptase (RT) and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), a unifying mechanism of inhibition remains elusive. Here, we assessed the inhibitory effects of FNC's active triphosphate form, FNC-TP, across several viral polymerases. The relative efficiency of FNC-TP incorporation followed the order: HIV-1 RT > hepatitis C virus (HCV) RdRp > respiratory syncytial virus (RSV) RdRp > dengue virus type 2 (DENV-2) RdRp ≫ SARS-CoV-2 RdRp. Its incorporation caused chain-termination in all polymerases tested. Antiviral activity against HIV-1 has previously been demonstrated and is here shown with DENV-2. Collectively, the data show that inhibition of viral polymerases by FNC-TP can translate to antiviral activity against both retroviruses and RNA viruses, but the link is not evident for SARS-CoV-2. FNC-TP is a poor substrate for SARS-CoV-2 RdRp, and FNC lacks significant antiviral activity against SARS-CoV-2 in cell culture.

Identifiers

PMID40900943
PMCPMC12400934

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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 Socratic graph.