Development of a Receptor Model for Efficient in silico Screening of HIV-1 Integrase Inhibitors

QUEVEDO, M.A.; RIBONE, S.R.; BRIÑÓN, M.C.; DEHAEN, W.

ELSEVIER SCIENCE INC

Lugar: New York; Año: 2014 vol. 52 p. 82 - 82

ntegrase (IN) is a key viral enzyme for the replication of the type-1 human immunodeficiency virus (HIV-1), and as such constitutes a relevant therapeutic target for the development of anti-HIV agents. However, the lack of crystallographic data of HIV IN complexed with the corresponding viral DNA has historically hindered the application of modern structure-based drug design techniques to the discovery of new potent IN inhibitors (INIs). Consequently, the development and validation of reliable HIV IN structural models that may be useful for the screening of large databases of chemical compounds is of particular interest. In this study, four HIV-1 IN homology models were evaluated respect to their capability to predict the inhibition potency of a training set comprising 36 previously reported INIs with IC50 values in the low nanomolar to the high micromolar range. Also, 9 inactive structurally related compounds were included in this training set. In addition, a crystallographic struc