title: In silico structure-based design and synthesis of novel anti-RSV compounds.
abstract: Respiratory syncytial virus (RSV) is the major cause for respiratory tract disease in infants and young children. Currently, no licensed vaccine or a selective antiviral drug against RSV infections are available. Here, we describe a structure-based drug design approach that led to the synthesis of a novel series of zinc-ejecting compounds active against RSV replication. 30 compounds, sharing a common dithiocarbamate moiety, were designed and prepared to target the zinc finger motif of the M2-1 protein. A library of ∼ 12,000 small fragments was docked to explore the area surrounding the zinc ion. Among these, seven ligands were selected and used for the preparation of the new derivatives. The results reported here may help the development of a lead compound for the treatment of RSV infections.
authors.affiliation: Medicinal Chemistry, School of Pharmacy & Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.
authors.forename: Michela
authors.initials: M
authors.lastname: Cancellieri
authors.affiliation: Medicinal Chemistry, School of Pharmacy & Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.
authors.forename: Marcella
authors.initials: M
authors.lastname: Bassetto
authors.affiliation: Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Ivy
authors.initials: I
authors.lastname: Widjaja
authors.affiliation: Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: van Kuppeveld
authors.affiliation: Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors.forename: Cornelis A M
authors.initials: CA
authors.lastname: de Haan
authors.affiliation: Medicinal Chemistry, School of Pharmacy & Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK. Electronic address: brancalea@cardiff.ac.uk.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancale
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D003198:Computer Simulation; D017076:Computer-Aided Design; D015195:Drug Design; D005028:Ethylenebis(dithiocarbamates) / Q000737:chemistry; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*; D016335:Zinc Fingers / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D005028:Ethylenebis(dithiocarbamates); D014764:Viral Proteins; D015032:Zinc
keywords: Antiviral; Respiratory syncytial virus; Structure-based virtual screening; Zinc-ejecting compounds