Tatsuya Takagi
Osaka University
Japan
Title: Screening novel HIV-1 inhibitors targeting cyclophilin A by structure-based and ligand-based in silico study
Biography
Biography: Tatsuya Takagi
Abstract
Since cyclophilin A has peptidyl-prolyl isomerase activity and binds to the capsid protein of Human Immunodeficiency Virus (HIV), it is an attractive target as an anti-HIV drug. However, just a few drugs against HIV-1 infection targeting cyclophilin A have been developed and none of them has been approved. We found a number of active compounds by in silicon structure-based screenings applying to the database with 1, 300 compounds recently. Although we found three docking sites A, B, and C, using MOE alpha site finder module, we used all of them as the docking sites because the three pockets were small. Two compounds, 12 and 23, were obtained as the most active ones. 12 covered the two docking sites, B and C, by cation-π interactions while the other covered B and C by CH-π and hydrogen bond. Especially, both of them exhibited anti-HIV activity against viral replication at low concentrations and relatively low cytotoxicity at the effective concentrations inhibiting viral growth by 50 %. As the results of comparisons between the obtained two compounds and the two controls which were called D4 and FD8, our compounds showed better results.