Structural biology in antiviral drug discovery.
Structural biology has emerged during the last thirty years as a powerful tool for rational drug discovery. Crystal structures of biological targets alone and in complex with ligands and inhibitors provide essential insights into the mechanisms of actions of enzymes, their conformational changes upon ligand binding, the architectures and interactions of binding pockets. Structure-based methods such as crystallographic fragment screening represent nowadays invaluable instruments for the identification of new biologically active compounds. In this context, three-dimensional protein structures have played essential roles for the understanding of the activity and for the design of novel antiviral agents against several different viruses. In this review, the evolution in the resolution of viral structures is analysed, along with the role of crystal structures in the discovery and optimisation of new antivirals.
School of Pharmacy & Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.
Marcella
M
Bassetto
Dipartimento di Scienze del Farmaco, Università degli Studi del Piemonte Orientale A, Avogadro Largo Donegani 2, 28100 Novara, Italy.
Alberto
A
Massarotti
Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
Antonio
A
Coluccia
School of Pharmacy & Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK. Electronic address: brancalea@cardiff.ac.uk.
Andrea
A
Brancale
D000998:Antiviral Agents / Q000494:pharmacology*; D003461:Crystallography / Q000379:methods; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008024:Ligands; D011487:Protein Conformation; D011506:Proteins / Q000494:pharmacology; D014777:Virus Diseases / Q000188:drug therapy / Q000821:virology; D014780:Viruses / Q000187:drug effects
D000998:Antiviral Agents; D008024:Ligands; D011506:Proteins