<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Vrancken, R</style></author><author><style face="normal" font="default" size="100%">Paeshuyse, J</style></author><author><style face="normal" font="default" size="100%">Andy Haegeman</style></author><author><style face="normal" font="default" size="100%">Puerstinger, G</style></author><author><style face="normal" font="default" size="100%">Froeyen, M</style></author><author><style face="normal" font="default" size="100%">Herdewijn, P</style></author><author><style face="normal" font="default" size="100%">Pierre Kerkhofs</style></author><author><style face="normal" font="default" size="100%">Neyts, J</style></author><author><style face="normal" font="default" size="100%">F. Koenen</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Imidazo[4,5-c]pyridines inhibit the in vitro replication of the classical swine fever virus and target the viral polymerase.</style></title><secondary-title><style face="normal" font="default" size="100%">Antiviral Res</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Antiviral Res.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Amino Acid Substitution</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antiviral Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line</style></keyword><keyword><style  face="normal" font="default" size="100%">Classical swine fever virus</style></keyword><keyword><style  face="normal" font="default" size="100%">Diarrhea Viruses, Bovine Viral</style></keyword><keyword><style  face="normal" font="default" size="100%">Drug Resistance, Viral</style></keyword><keyword><style  face="normal" font="default" size="100%">Imaging, Three-Dimensional</style></keyword><keyword><style  face="normal" font="default" size="100%">Imidazoles</style></keyword><keyword><style  face="normal" font="default" size="100%">Inhibitory Concentration 50</style></keyword><keyword><style  face="normal" font="default" size="100%">Models, Molecular</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Structure</style></keyword><keyword><style  face="normal" font="default" size="100%">polymerase chain reaction</style></keyword><keyword><style  face="normal" font="default" size="100%">Pyridines</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA Replicase</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Viral</style></keyword><keyword><style  face="normal" font="default" size="100%">Sequence Analysis, DNA</style></keyword><keyword><style  face="normal" font="default" size="100%">Structure-Activity Relationship</style></keyword><keyword><style  face="normal" font="default" size="100%">Virus Replication</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2008</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2008 Feb</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">77</style></volume><pages><style face="normal" font="default" size="100%">114-9</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Selective inhibitors of the replication of the classical swine fever virus (CSFV) may have the potential to control the spread of the infection in an epidemic situation. We here report that 5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP) is a highly potent inhibitor of the in vitro replication of CSFV. The compound resulted in a dose-dependent antiviral effect in PK(15) cells with a 50% effective concentration (EC(50)) for the inhibition of CSFV Alfort(187) (subgroup 1.1) of 1.6+/-0.4 microM and for CSFV Wingene (subgroup 2.3) 0.8+/-0.2 microM. Drug-resistant virus was selected by serial passage of the virus in increasing drug-concentration. The BPIP-resistant virus (EC(50): 24+/-4.0 microM) proved cross-resistant with VP32947 [3-[((2-dipropylamino)ethyl)thio]-5H-1,2,4-triazino[5,6-b]indole], an unrelated earlier reported selective inhibitor of pestivirus replication. BPIP-resistant CSFV carried a T259S mutation in NS5B, encoding the RNA-dependent RNA-polymerase (RdRp). This mutation is located near F224, a residue known to play a crucial role in the antiviral activity of BPIP against bovine viral diarrhoea virus (BVDV). The T259S mutation was introduced in a computational model of the BVDV RdRp. Molecular docking of BPIP in the BVDV polymerase suggests that T259S may have a negative impact on the stacking interaction between the imidazo[4,5-c]pyridine ring system of BPIP and F224.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/17997169?dopt=Abstract</style></custom1></record></records></xml>