ICARST in collaboration with Faculty of Pharmacy and Faculty of Natural Sciences of Comenius University in Bratislava has received approval and funding of the new research project proposal aimed at research in the development of inhibitors of influenza A virus neuraminidase entitled "Computational design, synthesis, testing and disposition of inhibitors of neuraminidazes of influenza A virus as potential antiviral compounds".
Influenza epidemics represent a constant threat to human health throughout the globe. Emergence of highly pathogenic strains of influenza A virus, such as avian influenza H5N1 from 2003, and others, capable of direct animal-to-human transmission calls for the development of more potent antiviral drugs to be used for the prophylaxis and treatment of a possible influenza pandemic. In this project, we propose to use rational computer-assisted drug design, development of new unique synthetic strategies, activity testing of new analogs in neuraminidase inhibition assays as well as development of drug-delivery systems. Analogs containing phospho and sulfo isosters of the key carboxyl group, stereoisomers and other derivatives of the antiviral drugs: oseltamivir, zanamivir, peramivir and laninamivir approved for treatment of influenza, will be designed to inhibit neuraminidase subtypes N1, N3, N7 and N9 of the influenza A virus. Promising compounds will be synthesized, tested for inhibitory potency and selected for further pharmaceutical development. Both compounds specific to individual neuraminidase subtypes as well as compounds with wider spectrum of activities against the panel of neuraminidase isoforms will be considered. In addition, we will develop lipid-based drug-delivery systems which will ensure increased oral bioavailability of the designed inhibitors also for derivatives of antivirotics that are at present available only by inhalation or intravenous routes.