RNA viruses are a major cause of disease that in the last fifteen years counted for frequent outbreaks, infecting both humans and animals. Examples of emerging or ri-emerging viral pathogens are the Foot-and- Mouth disease virus (FMDV) for animals, Chikungunya virus (CHIKV), Coxsackie virus B3 (CVB3) and Respiratory Syncytial virus (RSV) for humans, all responsible for infections associated with mild to severe complications. Although both vaccines and small-molecule compounds are at different stages of development, no selective antiviral drugs have been approved so far, therefore for all four these viruses improved treatment strategies are required. Promising targets are the viral non-structural proteins, which are commonly evaluated for the identification of new antivirals. Starting from the study of different viral proteins, several computer-aided techniques were applied, aiming to identify hit molecules first, and secondly to synthesise new series of potential antiviral compounds. The available crystal structures of some of the proteins that play a role in viral replication were used for structure- and ligand-based virtual screenings of commercially available compounds against CVB3, FMDV and RSV. New families of potential anti-CHIKV compounds were rationally designed and synthesized, in order to establish a structureactivity relationship study on a lead structure previously found in our group. Finally, a de-novo drug design approach was performed to find a suitable scaffold for the synthesis of a series of zinc-ejecting compounds against RSV. Inhibition of virus replication was evaluated for all the new compounds, of which different showed antiviral potential.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:633576 |
| Date | January 2014 |
| Creators | Cancellieri, Michela |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/69187/ |
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