Design of novel molecules that may be used as antivirals

The field of antiviral compound development is pivotal to combat viral diseases, with a special focus on compounds with a different mechanism of action compared to existing drugs. In particular, the inhibition of HSV attachment and/or entry is a main area of research of the group. Viral glycoproteins undergo several conformational rearrangements during the fusion process. Several domains buried in the prefusion structure may be exposed to the fusogenic structure and each of them may represent a potential target for the design of HSV inhibitors. Galdiero’s group studied in detail the structural basis of HSV membrane fusion and identified new targets of inhibition. We found that helical domains as well as surface loops may play an important role in the viral fusion process and represent possible targets of therapeutic interference. We observed that fusion peptides are able to inhibit viral fusion probably by intercalating with viral fusion peptides upon adopting functional structure in membranes, indicating that their inhibitory effects are a consequence of their ability to partition into membranes and aggregate within themselves.  Moreover, the analysis of the helical domains of the glycoprotein gB allowed both the achievement of a model for the conformational rearrangements that take place from the pre-fusion to the post-fusion structure and the development of promising first generation antiviral peptides.

The group is also involved in the investigation of the antiviral activity of functionalized poly(amide)-based dendrimers. The peptidodendrimer inhibits both HSV-1 and HSV-2 at a very early stage of the entry process, most likely through an interaction with the viral envelope glycoproteins; thus, preventing the virus from coming into close contact with cellular membranes, a prerequisite of viral internalization. These results show that the functionalization of a dendrimer with the peptide sequence derived from an HSV glycoprotein holds promising inhibitory activity towards viruses of the Herpesviridae family.


Understanding the penetration mechanism of enveloped viruses


Design of novel molecules that may be used as antibacterials


Drug delivery