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In Vitro Antiviral Activity of New Oxazoline Derivatives as Potent Poliovirus Inhibitors

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journal contribution
posted on 04.12.2018, 00:00 by Valentina Noemi Madia, Antonella Messore, Luca Pescatori, Francesco Saccoliti, Valeria Tudino, Alessandro De Leo, Luigi Scipione, Lucia Fiore, Eric Rhoden, Fabrizio Manetti, M. Steven Oberste, Roberto Di Santo, Roberta Costi
The final stages of polio eradication are proving more difficult than the early phases, and the development of effective drugs and treatments is considered a priority; thus, the research is ongoing. A screening of our in-house chemical library against poliovirus Sabin strains led to the identification of compounds 5 and 6 as hits active at submicromolar concentrations. Derivatives of these compounds were synthesized as a preliminary structure–activity-relationship study. Among them, 7 and 11 were highly active against poliovirus Sabin 1–3. Compound 11 was also very potent against a large panel of wild and vaccine-derived polioviruses. Time-of-addition experiments suggest that 5 and 7 could be active at an early stage of viral replication, whereas 11 was active at same concentration at all stages of viral replication. A ligand-based approach was applied to find the common structural features shared by the new compounds and already-known poliovirus inhibitors.