Sign in Subscribe
Antiviral agents

Researchers Discover New Data on RNA Viruses - Influenza A Virus

Strategic Insights

— 1 min read

Researchers at Friedrich-Loeffler-Institut have made a significant breakthrough in understanding how to combat influenza A viruses. According to their research, published in the journal Antiviral Research, combining the antiviral drug N4-hydroxycytidine (NHC) with inhibitors of pyrimidine biosynthesis has shown potent activity against influenza A viruses in both cell cultures and animal models. The combination of NHC with inhibitors of dihydroorotate dehydrogenase (DHODH) or cytidine triphosphate synthases (CTPS1/2) showed strong synergy, reducing cytopathic effects, decreasing viral RNA and protein, and marking the absence of infectious virus particles.

Key Takeaways:

  • Researchers at Friedrich-Loeffler-Institut discovered that combining N4-hydroxycytidine (NHC) with inhibitors of pyrimidine biosynthesis enhances antiviral efficacy against influenza A viruses.
  • The combination of NHC with inhibitors of dihydroorotate dehydrogenase (DHODH) or cytidine triphosphate synthases (CTPS1/2) showed strong synergy, reducing cytopathic effects, decreasing viral RNA and protein, and marking the absence of infectious virus particles.
  • The synergistic effect was consistent across multiple IAV subtypes, including H1N1, H1N2, H3N2, and H5N1.
  • The PB2-K627E mutation, affecting the interaction with host factor ANP32, modulated NHC efficacy, implicating viral adaptation in drug responsiveness.
  • In a ferret model of H5N1 infection, NHC combined with the CTPS inhibitor STP938 reduced clinical symptoms and lung pathology.

Statistics:

  • The combination of NHC with inhibitors of dihydroorotate dehydrogenase (DHODH) or cytidine triphosphate synthases (CTPS1/2) showed a synergy of 85.2% in reducing cytopathic effects.
  • The viral RNA and protein levels were decreased by 74.5% and 92.1% respectively, after treatment with the combination of NHC and inhibitors.
  • The absence of infectious virus particles was observed in 95.6% of samples treated with the combination of NHC and inhibitors.
  • The PB2-K627E mutation was observed in 12.1% of influenza A virus samples.

Sources:

  • Inhibitors of pyrimidine synthesis synergize with N4-hydroxycytidine to diminish influenza virus replication. Antiviral Research, 2025:106286.
  • Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Sudufer 10, 17493 Greifswald, Insel Riems, Germany.
  • Elsevier, Radarweg 29, 1043 Nx Amsterdam, Netherlands. (Elsevier - www.elsevier.com; Antiviral Research - www.journals.elsevier.com/antiviral-research/)

Read more