Understanding the function of key proteins found in influenza viruses could lead to broad spectrum flu drugs, according to scientists in the US.

Lawrence Pinto and Robert Lamb at Northwestern University studied the function of the M2 protein in the life cycle of the influenza A virus subtype. Four M2 proteins combine to form a pore in the virus membrane that conducts ions. The M2 proteins and ion channels differ greatly among subtypes of influenza virus but Pinto and Lamb have identified parts of the viral protein that all subtypes share.

The M2 ion channel allows protons to enter the viral particle and so lower its internal pH. This acidifying step is a prerequisite for viral replication, said Pinto: it enables the virus to release genetic material into the host cell, where it uses the cell machinery to replicate itself. 

The antiviral drug amantadine works by disabling the M2 protein and hence preventing viral replication. However, amantadine is effective only against influenza type A, and viruses can gain resistance to its effects. Pinto suggests that a drug targeted against the features common to all subtypes of the virus might be more useful than amantadine in inhibiting replication. 

'The battle with the influenza virus is far from over,' said Pinto. The H5N1 subtype of the influenza A virus ('bird flu'), first discovered in birds in Asia, has recently spread to Europe and Africa and influenza remains a persistent threat to public health. 'At present only one drug, oseltamivir, is capable of inhibiting the H5N1 subtype and more inhibitors are needed,' said Pinto. 

'The discovery of antiviral drugs historically has been largely fortuitous,' said Fei Philip Gao, a scientist at Florida State University. 'Detailed knowledge of the structure and dynamics of this protein will enhance our ability to design better inhibitors,' said Gao. 

Chris Gandhi, a research fellow at the California Institute of Technology, agrees: 'if you can find a single compound that selectively blocks M2 from every strain, the whole viral life cycle would be disrupted. That's not a trivial task, but it's worth pursuing.' 

Debora Giovanelli