Translocation of viral integrase (IN) into the nucleus is a critical precondition of integration during the life cycle of HIV, a causative agent of Acquired Immunodeficiency Syndromes (AIDS). As the first discovered cellular factor to interact with IN, Lens epithelium-derived growth factor (LEDGF/p75) plays an important role in the process of integration. Disruption of the LEDGF/p75-IN interaction has provided a great interest for anti-HIV agent discovery. In this work, we reported that one small molecular compound, 1,4-bis(5-(naphthalen-1-yl)thiophen-2-yl)naphthalene(Compound 15), potently inhibit the IN-LEDGF/p75 interaction and affect the HIV-1 IN nuclear distribution at 1 μM. The putative binding mode of Compound 15 was constructed by a molecular docking simulation to provide structural insights into the ligand-binding mechanism. Compound 15 suppressed viral replication by measuring p24 antigen production in HIV-1IIIB acute infected C8166 cells with EC50 value of 11.19 μM. Compound 15 might supply useful structural information for further anti-HIV agent discovery.
Bibliographical noteFunding Information:
This work was partially supported by the Research Fund for the Control of Infectious Diseases from Hong Kong to DCCW (08070152), the National Natural Science Foundation of China (81102483; 81001462; 81360503), 973 Program (2009CB522306) and the Key Scientific and Technological Program of China (2012ZX10001-006, 2012ZX10001-007) and Yunnan (2010GA001).
Copyright 2014 Elsevier B.V., All rights reserved.
- HIV-1 integrase
- Lens epithelium-derived growth factor (LEDGF/P75)
- Molecular docking