MAPPIT as a high-throughput screening assay for modulators of protein-protein interactions in HIV and HCV.
The discovery of novel antivirals for HIV and HCV has been a focus of intensive research for many years. Where the inhibition of critical viral enzymes by small molecules has proven effective for many viruses, there is considerable merit in pursuing protein-protein interactions (PPIs) as targets for therapeutic intervention. The mammalian protein-protein interaction trap (MAPPIT) is a two-hybrid system used for the study of PPIs. The bait and prey proteins are linked to deficient cytokine receptor chimeras, where the bait and prey interaction and subsequent ligand stimulation restores JAK-STAT signaling, resulting in reporter gene expression controlled by a STAT3-responsive promoter. We report the use of MAPPIT as a high-throughput screening assay for the discovery of inhibitors or stimulators of the Vif-APOBEC3G interaction and the reverse transcriptase heterodimerization (RTp66-RTp51) for HIV and the NS4A-NS3 interaction for HCV.
Tibotec Inc, Mechelen, Belgium.
Bertrand
B
Van Schoubroeck
Koen
K
Van Acker
Géry
G
Dams
Dirk
D
Jochmans
Reginald
R
Clayton
Jan Martin
JM
Berke
Sam
S
Lievens
José
J
Van der Heyden
Jan
J
Tavernier
D004353:Drug Evaluation, Preclinical / Q000379:methods*; D057809:HEK293 Cells; D006678:HIV / Q000378:metabolism*; D016174:Hepacivirus / Q000378:metabolism*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D011485:Protein Binding / Q000187:drug effects; D060066:Protein Interaction Maps / Q000187:drug effects*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D015203:Reproducibility of Results; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism
D014764:Viral Proteins