Background

THE NEED FOR NEW ANTI-INFLUENZA DRUGS

In recent years the serious threat posed by influenza virus to worldwide public health has been highlighted firstly, by the ongoing low level transmission of the highly pathogenic avian H5N1 strain to humans (63% mortality in infected humans)  and secondly, by the unexpected emergence in 2009 of a novel pandemic strain A/H1N1, which rapidly spread around the entire world. Whilst this new H1N1 strain is currently highly contagious but results in only mild illness, the future evolution of this virus is unpredictable. H5N1 might have just as easily become more readily transmissible between humans. Similarly, the new A/H1N1 might have been more virulent, or could have acquired the single point mutation that confers Tamiflu resistance, in the same way as many seasonal H1N1 strains have recently done.

In such scenarios, the time needed to generate and deploy a vaccine (~6 months in the relatively favourable case of A/H1N1 and still not a solved problem for H5N1) could have been catastrophically costly in terms of human lives and societal disruption. One could rightly say that mankind has been lucky so far.

It is widely acknowledged that a broader choice of anti-influenza drugs is needed to treat people before a new vaccine becomes available, to treat severe influenza cases generally, as well as to counter the problem of viral resistance. In a letter published in Science on 20/3/09 several eminent virologists stated “whatever strategies are adopted, it is clear that additional anti-influenza therapeutics are urgently needed. So far, vaccines and antivirals have targeted three influenza envelope proteins: hemagglutinin, neuraminidase, and the M2 ion channel protein. We need new classes of antivirals that interfere with other necessary viral processes (e.g., polymerase complex activity, interferon antagonist activity, and viral assembly”).

The development of new anti-influenza drugs, which had been neglected by major pharmaceutical companies in the wake of anti-neuraminidase drugs becoming available, has once again become a high priority.