Broad antiviral compounds targeting viral envelope: synthesis and pre-clinical studies.

The majority of viral pathogens that cause emerging and re-emerging infectious diseases are membrane-enveloped viruses. In this thesis work a new series of antiviral compounds, with 1H-pyrrol-methylene thioxodihydropyrimidine structure, were designed and synthesized. They were endowed with antiviral activity on enveloped viruses, likely ZIKAV, DENV-2, and five influenza virus strains, including the pandemic H7N9 model. The intriguing mechanism of action was pursued and confirmed the hypothesis of compounds able to intercalate in the viral lipid envelope membrane and to oxidize phospholipids, impairing the physical and chemical structure of the viral membrane and impacting the fusion of viral and cell membranes. With the aim of investigating in vitro and in vivo pre-clinical features, compounds were assayed for their chemical-physical properties. Finally, a preliminary in vivo PK was assessed.