For treatment-naive adult patients infected with HIV, the first-line antiretroviral regimen consists of 2 nucleoside reverse transcriptase inhibitors in combination with an integrase inhibitor or a boosted darunavir regimen.1 As of April 2015, the US Department of Health and Human Services replaced atazanavir with an alternative protease inhibitor regimen in its guidelines for adults and adoles...

Acquired immunodeficiency syndrome (AIDS) is a formidable pandemic that is still creating havoc world-wide. The curative agent of this disease has been found to be a virus called human immunodeficiency virus of type-1 (HIV-1). In the replicative cycle of HIV-1, the integration of the viral DNA into host chromosomes is an essential step that is catalyzed by the enzyme integrase (IN). Inhibition ...

HIV-1 integrase (IN) is the target for two classes of antiretrovirals: i) the integrase strand-transfer inhibitors (INSTIs) and ii) the non-catalytic site integrase inhibitors (NCINIs). NCINIs bind at the IN dimer interface and are thought to interfere primarily with viral DNA (vDNA) integration in the target cell by blocking IN-vDNA assembly as well as the IN-LEDGF/p75 interaction. Herein we s...

Acquired immunodeficiency syndrome (AIDS) is a formidable pandemic that is still creating havoc world-wide. The curative agent of this disease has been found to be a virus called human immunodeficiency virus of type-1 (HIV-1). In the replicative cycle of HIV-1, the integration of the viral DNA into host chromosomes is an essential step that is catalyzed by the enzyme integrase (IN). Inhibition ...

Among several biological targets to treat AIDS, HIV integrase is a promising enzyme that can be employed to develop new anti-HIV agents. The aim of this work is to propose a mechanistic interpretation of HIV-1 integrase inhibition and to rationalize the molecular features related to the binding affinity of studied ligands. A set of 79 HIV-1 integrase inhibitors and its relationship with biologi...

UNLABELLED During virion maturation, HIV-1 capsid protein assembles into a conical core containing the viral ribonucleoprotein (vRNP) complex, thought to be composed mainly of the viral RNA and nucleocapsid protein (NC). After infection, the viral RNA is reverse transcribed into double-stranded DNA, which is then incorporated into host chromosomes by integrase (IN) catalysis. Certain IN mutatio...

This July 2014 edition of the IAS-USA drug resistance mutations list updates the figures last published in March 2013. The following mutations have been added to existing classes or drugs: K65E/N has been added to the bars for the nucleoside and nucleotide analogue reverse transcriptase inhibitors (nRTIs) abacavir, didanosine, emtricitabine, lamivudine, stavudine, and tenofovir; L100I has been ...

Protein-protein interactions (PPIs) can be considered as a vast class of therapeutic targets. PPIs play critical roles in all biological functions and are often dysregulated in disease. Despite their functional role both inside and outside the cell, over the past decades PPIs have been neglected as undruggable targets. This was in part due to the fact that PPI interfaces are generally flat and ...