Design, synthesis and molecular mechanism of few neuraminidase inhibitors in treatment of H1N1 by NMR techniques

Considering the issue of resistance to anti-influenza drugs, there is a need for discovery of new antiviral drugs. In view of this, flavones and their synthetic precursors i.e. chalcones were designed as inhibitors of influenza virus - H1N1 neuraminidase enzyme using structure-based drug design. Based on the best docking scores, some chalcone and flavone derivatives were synthesized and characterized by IR and proton NMR. Few of them were selected for 31P NMR studies, in order to probe the molecular mechanism of their antiviral action. Reasonably good correlation between docking scores and 31P NMR results were observed. As antiviral drugs are known to show membrane stabilizing effect on host cell, 31P NMR data for methoxy chalcone showed stabilization effect on model membrane pointing towards good antiviral activity which remained unaffected even after its cyclization to flavone. These derivatives can be explored further to provide a future therapeutic option for the treatment and prophylaxis of H1N1 viral infections.