Inhibitors of HIV-1 Entry and Integration: Recent Developments and Impact on Treatment

Anil K.      Sharma; Varghese      George; Ranjini      Valiathan; Sudheesh      Pilakka-Kanthikeel; Suresh      Pallikkuth

Abstract

Advances in the drug development against HIV-1 have lead to the identification of new compounds which could be used to target cellular entry and nuclear integration of virus in addition to drugs that commonly target reverse transcriptase and protease. These additional targets have added a new dimension to fight against HIV. Cellular entry of HIV is a multistep procedure involving a range of cellular and molecular interactions between virus envelope protein and receptors expressed on the surface of the target cells, thus providing many opportunities to block infection. Some of these entry inhibitors are currently being used in the clinic and more compounds are under various stages of development. Integration of the HIV-1 DNA is required and essential to maintain the viral DNA in the infected cell. The design and discovery of integrase inhibitors were first focused at targeting the catalytic site of integrase that selectively acting on strand transfer and thus inhibits integration of virus DNA with host cell genome. Thus, entry and integrase inhibitors present a real added value in combined treatment against HIV infection. This review discusses the recent development in the discovery of inhibitors of HIV entry and integration along with some of recent patents in the field.

Keywords: ART, entry inhibitors, HIV, HIV-1, HIV patents, HIV treatment, integrase inhibitors, Raltegravir.