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

ingentiumby ingentium

In Coronavirus Literature.

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

Publication date: Jul 01, 2025

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.

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Concepts Keywords
Antiviral Activity
Efficiency Antiviral
Immunodeficiency Azvudine
Polymerase Cov
Retroviruses Fnc
Hiv
Inhibition
Mechanism
Polymerases
Rdrp
Sars
Spectrum
Tp
Viral
Virus

Semantics

Type Source Name
disease MESH coronavirus disease 2019
drug DRUGBANK Cytidine
disease MESH infection
disease IDO cell
drug DRUGBANK Ilex paraguariensis leaf
disease MESH Inflammation
disease IDO immunodeficiency
disease MESH syndrome
disease MESH hepatitis
pathway REACTOME Reproduction
drug DRUGBANK Coenzyme M
pathway REACTOME Translation
disease IDO site
drug DRUGBANK Adenosine
disease MESH influenza
disease MESH alphavirus infections
drug DRUGBANK Uridine
drug DRUGBANK Tretamine
drug DRUGBANK Tromethamine
drug DRUGBANK Potassium Chloride
drug DRUGBANK Sucrose
drug DRUGBANK Imidazole
drug DRUGBANK Glycerin
drug DRUGBANK Sodium lauryl sulfate
disease IDO facility
disease IDO nucleic acid
drug DRUGBANK Timonacic
drug DRUGBANK 2′-Deoxycytidine 5′-triphosphate
drug DRUGBANK Edetic Acid
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Aspartame
drug DRUGBANK Cefaclor
drug DRUGBANK Streptomycin
drug DRUGBANK Dimethyl sulfoxide
drug DRUGBANK Bortezomib
disease MESH virus Infections
drug DRUGBANK Formaldehyde
drug DRUGBANK Phosphate ion
drug DRUGBANK Amphotericin B
drug DRUGBANK Cysteamine
drug DRUGBANK Activated charcoal
disease IDO replication
drug DRUGBANK Cytarabine
disease IDO assay
disease MESH dissociation
drug DRUGBANK Urea
drug DRUGBANK Cytidine-5′-Monophosphate
disease IDO susceptibility
drug DRUGBANK Uridine monophosphate
drug DRUGBANK L-Phenylalanine
drug DRUGBANK Lamivudine
drug DRUGBANK L-Valine
drug DRUGBANK Glycine
pathway KEGG Viral replication
drug DRUGBANK Ritonavir
disease MESH ARC
drug DRUGBANK 3 7 11 15-Tetramethyl-Hexadecan-1-Ol
disease MESH Allergy
disease MESH Infectious Diseases
disease MESH emergency
drug DRUGBANK Troleandomycin
disease MESH Middle East respiratory syndrome
disease MESH respiratory syncytial virus infection
disease MESH avian influenza
disease IDO production
disease IDO protein
disease IDO host
disease IDO pathogen
drug DRUGBANK Guanosine
drug DRUGBANK Favipiravir
drug DRUGBANK Stavudine
drug DRUGBANK L-Glutamine
drug DRUGBANK Alpha-Linolenic Acid
disease MESH Mutation rates
drug DRUGBANK Zidovudine
drug DRUGBANK Diflunisal
drug DRUGBANK Adefovir
drug DRUGBANK Tenofovir
drug DRUGBANK Emtricitabine
drug DRUGBANK Abacavir
drug DRUGBANK Elvitegravir
drug DRUGBANK Cobicistat
disease MESH AIDS
drug DRUGBANK R1626
disease MESH chronic hepatitis
drug DRUGBANK Balapiravir
disease MESH dengue
drug DRUGBANK Ribavirin
disease MESH viral load
drug DRUGBANK Folic Acid

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