Rapid screening of chemical inhibitors that block processive DNA synthesis of herpesviruses: potential application to high-throughput screening.
Processivity factors associate with DNA polymerases, enabling them to incorporate thousands of nucleotides without dissociating from the template. The processivity factors encoded by each of the herpesviruses are ideal targets for specifically blocking viral replication, particularly since they have unique primary amino acid sequences. Here we provide details of a rapid mechanistic plate assay and its potential application to high-throughput screening of libraries of tens of thousands of chemical compounds to identify inhibitors of processive DNA synthesis. Methods of validation testing are presented.
Ricciardi
Robert P
RP
Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA.
Lin
Kai
K
Chen
Xulin
X
Dorjsuren
Dorjbal
D
Shoemaker
Robert
R
Sei
Shizuko
S
D004247:DNA / Q000096:biosynthesis*; D019288:Herpesvirus 8, Human / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D014764:Viral Proteins
D019384:Nucleic Acid Synthesis Inhibitors; C110348:ORF59 protein, Human herpesvirus 8; D014764:Viral Proteins; D004247:DNA