5-Bromo-2'-deoxyuridine inhibits African swine fever virus (ASFV) replication via interfering viral DNA replication and suppressing the formation of viral factories.

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  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 0110674 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0341 (Electronic) Linking ISSN: 00426822 NLM ISO Abbreviation: Virology Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, Academic Press.
    • Subject Terms:
      African Swine Fever Virus*/drug effects ; African Swine Fever Virus*/physiology ; African Swine Fever Virus*/genetics ; Virus Replication*/drug effects ; Antiviral Agents*/pharmacology ; DNA Replication*/drug effects ; African Swine Fever*/virology ; Bromodeoxyuridine*/pharmacology ; Bromodeoxyuridine*/metabolism ; Macrophages, Alveolar*/virology ; Macrophages, Alveolar*/drug effects ; DNA, Viral*/genetics; Animals ; Swine ; Cells, Cultured
    • Abstract:
      African swine fever (ASF), caused by ASF virus (ASFV), represents one of the most economically important viral infectious diseases in swine industry worldwide. So far there is no vaccine or antiviral drug for controlling ASF pandemics. In the present study, we assessed inhibition of six nucleoside analogues against ASFV replication in ex vivo primary porcine alveolar macrophages (PAMs), including the first approved antiviral drug idoxuridine. Our results showed that, out of the assessed six compounds, 5-Bromo-2'-Deoxyuridine (5-BrdU, an analog of idoxuridine), exhibited the strongest inhibition on the replication of ASFV in PAMs with a 50% inhibitory concentration (IC 50 ) value of 2.9 μM and a low cytotoxicity (CC 50  > 270 μM). Moreover, we showed that 5-BrdU interferes with ASFV DNA replication by incorporating into viral replicating DNA molecules as a competitive substrate for deoxythymidine, ultimately inhibiting the formation of ASFV viral factories. Altogether, our findings suggest that 5-BrdU could serve as a promising therapeutic agent for combating ASFV infection.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: 5-Bromo-2′-Deoxyuridine (5-BrdU); African swine fever virus (ASFV); Anti-ASFV activity; Virus factory
    • Accession Number:
      0 (Antiviral Agents)
      G34N38R2N1 (Bromodeoxyuridine)
      0 (DNA, Viral)
    • Publication Date:
      Date Created: 20240917 Date Completed: 20241110 Latest Revision: 20241110
    • Publication Date:
      20241114
    • Accession Number:
      10.1016/j.virol.2024.110237
    • Accession Number:
      39288610