Novel drugs to fight influenza
Influenza virus infections occur in seasonal epidemics, resulting in millions of cases of severe illness and hundreds of thousands estimated annual deaths. In addition to these seasonal epidemics, highly virulent strains emerged during several pandemics, such as the Spanish Flu of 1918. Vaccination is currently the primary means of controlling the spread of influenza virus infections, but due to the virus' notorious ability to mutate, new vaccines must be developed each year. The key objective of the EU-funded ′Development of novel antiviral drugs against influenza′ (Flucure) project is to develop innovative therapeutics against influenza by targeting the viral ribonucleoprotein (RNP) complex, a major contributor to viral virulence. The high level of conservation of the RNP complex, combined with slow mutation rates, should result in therapeutics with broad viral strain specificity associated with a reduced risk for developing resistance. Through iterative cycles of hypothesis-driven molecular design, organic synthesis, and pharmacological evaluation of structural analogues of lead molecules, scientists have come up with various lead candidates. The consortium is employing three-dimensional pharmacophore models to define the structural requirements of the ligands to bind the targeted sites of action. Using this approach, over 500 novel molecules have been designed and the most promising candidates will be synthesised. Much effort is also being devoted to establishing biophysical assays that would help reveal how these compounds interfere with the RNP complex. Co-crystallisation experiments will determine their exact site and mode of binding. So far, the work of the Flucure project has yielded a new compound targeting the influenza nucleoprotein with high antiviral activity, resulting in a patent application. Given the magnitude of the influenza health problem globally, the Flucure deliverables potentially will have important consequences for protecting the health of European citizens. The broad applicability of the Flucure treatment approach means that in the event of a serious pandemic involving a highly pathogenic virus such as H5N1, affected individuals could be treated even before the exact nature of the viral strain will have been determined.