Background: Influenza viruses cause severe upper respiratory illness in children and the
elderly during seasonal epidemics. Influenza viruses from zoonotic reservoirs can also cause pandemics
with significant loss of life in all age groups. Although vaccination is one of the most effective
methods to protect against seasonal epidemics, seasonal vaccines vary in efficacy, can be ineffective in
the elderly population, and do not provide protection against novel strains. Small molecule therapeutics
are a critical part of our antiviral strategies to control influenza virus epidemics and pandemics as
well as to ameliorate disease in elderly and immunocompromised individuals.
Objective: This review aims to summarize the existing antiviral strategies for combating influenza viruses,
the mechanisms of antiviral resistance for available drugs, and novel therapeutics currently in
Methods: We systematically evaluated and synthesized the published scientific literature for mechanistic
detail into therapeutic strategies against influenza viruses.
Results: Current IAV strains have developed resistance to neuraminidase inhibitors and nearly complete
resistance to M2 ion channel inhibitors, exacerbated by sub-therapeutic dosing used for treatment
and chemoprophylaxis. New tactics include novel therapeutics targeting host components and combination
therapy, which show potential for fighting influenza virus disease while minimizing viral resistance.
Conclusion: Antiviral drugs are crucial for controlling influenza virus disease burden, but their efficacy
is limited by human misuse and the capacity of influenza viruses to circumvent antiviral barriers.
To relieve the public health hardship of influenza virus, emerging therapies must be selected for their
capacity to impede not only influenza virus disease, but also the development of antiviral resistance.