TY - JOUR
T1 - In silico structure-based design and synthesis of novel anti-RSV compounds
AU - Cancellieri, Michela
AU - Bassetto, Marcella
AU - Widjaja, Ivy
AU - van Kuppeveld, Frank
AU - de Haan, Cornelis A M
AU - Brancale, Andrea
AU - de Haan, C.A.M.
N1 - Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2015/8/8
Y1 - 2015/8/8
N2 - 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.
AB - 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.
U2 - 10.1016/j.antiviral.2015.08.003
DO - 10.1016/j.antiviral.2015.08.003
M3 - Article
C2 - 26259810
SN - 0166-3542
VL - 122
SP - 46
EP - 50
JO - Antiviral Research
JF - Antiviral Research
ER -