Drugs for influenza
Influenza can be tackled with antiviral drugs, though they have their limitations
- neuraminidase inhibitors – such as oseltamivir (Tamiflu) and zanamivir (Relenza) – which target the neuraminidase enzyme
- adamantanes – such as amantadine – which block ion transport through M2.
Neuraminidase inhibitors have fewer side-effects and are more effective. They are not cures: they shorten flu episodes by a couple of days, reduce the risk of complications and possibly lower the likelihood that someone will pass on the virus. Ideally, they should be given as early as possible in an infection and can also be used prophylactically (to prevent infection).
Resistance to oseltamivir has been detected in seasonal H1N1 strains and influenza A(H1N1)pdm09. All human strains of influenza virus are now resistant to amantadine, probably due to overuse, but are usually susceptible to neuraminidase inhibitors; some cases of oseltamivir resistance have been seen. Oseltamivir resistance has been seen in some human cases of H5N1 avian flu, although generally strains remain sensitive.
Because of the risk of resistance, it is much better to use drugs in combination. Other flu drugs are in development but, unfortunately, are years away from human use.
Drugs in development
Other neuraminidase inhibitors are in clinical trials, and may provide new options for people who acquire drug-resistant infections. Some drugs are being developed to target haemagglutinin but are at a very early stage of development.
Targeting host responses
An alternative approach is to use drugs that target host responses to infection, which actually cause the damage to tissues seen in disease. A wide range of drugs are being tested for use in flu, generally in combination with antivirals.
An innovative experimental strategy is to use RNA-based therapeutics. These are based on the principle of ‘RNA interference’ – binding a therapeutic RNA molecule to a target RNA molecule to create a double-stranded RNA molecule that triggers host cell defence mechanisms. The new molecule is degraded, preventing the viral RNA from generating viral proteins. One advantage of this approach is that multiple RNAs could be used to target a range of flu strains.Lead image:
Jon Large/Flickr CC BY NC
- Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel (2008)
- Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide (2007)
- Oseltamivir resistance during treatment of influenza A (H5N1) infection (2005)
- Antiviral resistance among highly pathogenic influenza A (H5N1) viruses isolated worldwide needs continued monitoring (2013)
- New treatments for influenza (2012)
- siRNA for influenza therapy
- Wikipedia: Neuraminidase inhibitor
- Wikipedia: Amantadine
Questions for discussion
- Which do you think are best for controlling influenza – drugs or vaccines?
- What are the benefits of drugs over vaccines?