background: gp41 of hiv (human immunodeficiency virus) is a protein that mediates fusion between viral and cellular membranes. the agent, t-20, which has been approved for hiv inhibition, can restrain gp41 function in the fusion process; nevertheless, it has disadvantages like instability, high cost of production and injection form to be delivered twice a day. methods: several molecules like nb...

Currently, there are about 37 million people worldwide living with human immunodeficiency virus (HIV) /AIDS, with an estimated two million new cases per year globally. According to estimates from the World Health Organization (WHO), only 75% of the population with HIV know their status. Initially, HIV infection was associated with significantly increased rates of mortality and morbidity. Howeve...

There are now 26 antiretroviral drugs and 6 fixed-dose combinations, including reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors and fusion (or entry) inhibitors, approved by the US Food and Drug Administration for clinical use. Although they are clinically effective when used in combination, none of the existing drugs are considered ideal because of toxic side effects...

The hydrophobic pocket in the HIV-1 gp41 N-terminal heptad repeat (NHR) domain plays an important role in viral fusion and entry into the host cell, and serves as an attractive target for development of HIV-1 fusion/entry inhibitors. The peptide anti-HIV drug targeting gp41 NHR, T-20 (generic name: enfuvirtide; brand name: Fuzeon), was approved by the U.S. FDA in 2003 as the first HIV fusion/en...

Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor antagonists for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 agonists as HIV-1 fusion inhibitors. A virus-free cell-based fusion reporter assay, based on mixing "effector cells" ...

HIV-1 integrase (IN) enzyme, one of the three main enzymes of HIV-1, catalyzed the insertion of the viral DNA into the genome of host cells. Because of the lack of its homologue in human cells and its essential role in HIV-1 replication, IN inhibition represents an attractive therapeutic target for HIV-1 treatment. Since identification of IN as a promising therapeutic target, a major progress h...

HIV-1 integrase (IN) enzyme, one of the three main enzymes of HIV-1, catalyzed the insertion of the viral DNA into the genome of host cells. Because of the lack of its homologue in human cells and its essential role in HIV-1 replication, IN inhibition represents an attractive therapeutic target for HIV-1 treatment. Since identification of IN as a promising therapeutic target, a major progress h...

Virions of the type 1 human immunodeficiency virus (HIV-1) can enter target cells by fusion or endocytosis, with sharply different functional consequences. Fusion promotes productive infection of the target cell, while endocytosis generally leads to virion inactivation in acidified endosomes or degradation in lysosomes. Virion fusion and endocytosis occur equally in T cells, but these pathways ...

Human immunodeficiency virus type 1 (HIV-1) fusion inhibitors blocking viral entry by binding the gp41 heptad repeat 1 (HR1) region offer great promise for antiretroviral therapy, and the first of these inhibitors, T20 (Fuzeon; enfuvirtide), is successfully used in the clinic. It has been reported previously that changes in the 3-amino-acid GIV motif at positions 36 to 38 of gp41 HR1 mediate re...

The use of synthetic peptides as HIV-1 inhibitors has been subject to research over recent years. Although the initial therapeutic attempts focused on HIV-coded enzymes, structural HIV proteins and, more specifically, the mechanisms that the virus uses to infect and replicate are now also considered therapeutic targets. The interest for viral fusion and entry inhibitors is growing significantly...