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Drugs in development for influenza.

David A Boltz1, Jerry R Aldridge, Robert G Webster

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Developing new influenza antivirals is crucial due to vaccine limitations and emerging drug resistance. This review covers investigational drugs targeting the virus or host for broader pandemic control.

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Area of Science:

  • Virology
  • Infectious Diseases
  • Drug Discovery

Background:

  • Influenza pandemics pose significant public health threats, with current control strategies like vaccines and antivirals having limitations.
  • Vaccine development lag time and safety concerns reduce their immediate effectiveness, while existing antivirals face emerging drug resistance.
  • The 2009 H1N1 pandemic highlighted the need for rapid and effective influenza control measures.

Purpose of the Study:

  • To review experimental data on novel antiviral agents for influenza.
  • To assess investigational drugs with broad reactivity against various influenza strains and subtypes.
  • To explore potential future therapeutic strategies, including combination drug therapy.

Main Methods:

  • Review of experimental data on antiviral agents in clinical trials and preclinical development.
  • Categorization of agents based on their mechanism of action (e.g., neuraminidase inhibitors, M2 inhibitors, polymerase inhibitors, haemagglutinin inhibitors, fusion inhibitors).
  • Examination of agents targeting viral components or host factors.

Main Results:

  • Several investigational antiviral agents are undergoing clinical trials, including parenteral zanamivir, peramivir, long-acting neuraminidase inhibitors, and favipiravir (T-705).
  • Experimental agents targeting viral proteins like haemagglutinin (cyanovirin-N, thiazolides) and host factors (DAS181, COX-2 inhibitors, PPAR agonists) show promise.
  • The development of broad-spectrum antivirals is essential due to the unpredictable nature of influenza epidemics and pandemics.

Conclusions:

  • Novel antiviral therapies are urgently needed to supplement vaccines and overcome resistance to existing drugs.
  • Investigational agents targeting diverse viral or host mechanisms offer potential for broad-spectrum influenza control.
  • Future strategies may involve combination antiviral therapy to enhance efficacy and prevent resistance.