Pharmacophore modeling, docking, and principal component analysis based clustering: combined computer-assisted approaches to identify new inhibitors of the human rhinovirus coat protein.
The development and application of a sophisticated virtual screening and selection protocol to identify potential, novel inhibitors of the human rhinovirus coat protein employing various computer-assisted strategies are described. A large commercially available database of compounds was screened using a highly selective, structure-based pharmacophore model generated with the program Catalyst. A docking study and a principal component analysis were carried out within the software package Cerius and served to validate and further refine the obtained results. These combined efforts led to the selection of six candidate structures, for which in vitro anti-rhinoviral activity could be shown in a biological assay.
Steindl
Theodora M
TM
Department of Pharmaceutical Chemistry, Institute of Pharmacy, and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 52c, A-6020 Innsbruck, Austria.
Crump
Carolyn E
CE
Hayden
Frederick G
FG
Langer
Thierry
T
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D036022:Capsid Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D002460:Cell Line; D003198:Computer Simulation; D003588:Cytopathogenic Effect, Viral; D016208:Databases, Factual; D006801:Humans; D008958:Models, Molecular; D025341:Principal Component Analysis; D012229:Rhinovirus / Q000737:chemistry* / Q000187:drug effects; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D036022:Capsid Proteins