Oseltamivir and neuraminidase inhibitors in influenza
Oseltamivir is a neuraminidase inhibitor: it blocks a viral enzyme and so stops new influenza virions (complete virus particles) being released from infected cells.
Remember
Neuraminidase inhibitors such as oseltamivir stop new influenza virions leaving infected cells, cover influenza A and B, and work best if started early, ideally within 48 hours of symptoms.
Influenza A and B viruses hook onto sialic acid (a sugar on the surface of the cells lining the airway) using a surface protein called haemagglutinin. Once the virus has replicated inside a cell, the new virions (complete virus particles) remain tethered to the cell by sialic acid bonds.
The viral enzyme neuraminidase cuts those bonds and frees the virions to infect neighbouring cells. Oseltamivir (Tamiflu) blocks this enzyme, so the virions stay stuck to the cell that made them and the infection spreads less readily. Haemagglutinin is how the virus hooks on at the start, and neuraminidase is how new virions get free at the end.
Oseltamivir is an oral prodrug (an inactive form that the body converts into the active drug). Zanamivir (Relenza) is the other neuraminidase inhibitor and is inhaled. It can cause bronchospasm (tightening of the airways), so it is best avoided in asthma. Both drugs are active against influenza A and B, and they work best if started early.
The aim of treatment is to reduce the duration and severity of illness. The drugs are used for treatment in high-risk patients, and for prophylaxis (using the drug to prevent infection) during outbreaks, for example in care homes. Amantadine and rimantadine work differently: they block the M2 ion channel (a proton channel in the virus), act on influenza A only and are largely abandoned because of resistance.
Key facts
- Target
- the viral enzyme neuraminidase, which cuts sialic acid bonds so that new virions can leave the cell.
- Timing
- the drugs are most effective when started within 48 hours of the first symptoms, so start them early.
- Drugs
- oral oseltamivir (Tamiflu) and inhaled zanamivir (Relenza), both active against influenza A and B.
- Side effects
- nausea, vomiting and abdominal pain with oseltamivir; bronchospasm with zanamivir.
- Pregnancy
- UK guidance makes oral oseltamivir first-line, with inhaled zanamivir second-line.
- Who is treated
- mainly high-risk patients, because the benefit is modest in healthy people.
Exam traps
- Amantadine and rimantadine block the M2 ion channel, which is not how oseltamivir works: oseltamivir inhibits neuraminidase, and unlike the M2 blockers it also works against influenza B.
- Oseltamivir does not block attachment through haemagglutinin, because it acts at the end of the cycle, on the release of new virions.
- Baloxavir marboxil is an endonuclease inhibitor, so it blocks an enzyme the virus needs to begin copying its RNA, and it does not stop finished virions being released.
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