A virus-dependent fusion assay was utilized to examine the activity of a panel of HIV-1, -2, and SIV isolates of distinct coreceptor phenotypes. This assay allowed identification of entry inhibitors, and characterization of an antagonist of a Rac guanine nucleotide exchange factor, as an inhibitor of HIV-mediated fusion.

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...

Peptides derived from the C-terminal heptad repeat (CHR) of HIV gp41 have been developed as effective fusion inhibitors against HIV-1, but facing the challenges of enhancing potency and stability. Here, we report a rationally designed novel HIV-1 fusion inhibitor derived from CHR-derived peptide (Trp628~Gln653, named CP), but with an innovative Ile-Asp-Leu tail (IDL) that dramatically increased...

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...

Human defensins are at the forefront of the host responses to HIV and other pathogens in mucosal tissues. However, their ability to inactivate HIV in the bloodstream has been questioned due to the antagonistic effect of serum. In this study, we have examined the effect of sub-inhibitory concentrations of human α-defensin HNP-1 on the kinetics of early steps of fusion between HIV-1 and target ce...

Several nonpeptide small molecules were designed as potential inhibitors of HIV protease and their structures were constructed by computer-aided molecular modeling and docked iwo the active site of HIV protease. Models of the complexes of inhibitors and the HIV protease were refined using nonbonded and H-bonding terms. The refined energy of selected complexes showed that the designed inhib...

SCH-C (SCH 351125) is a small-molecule antagonist of the human immunodeficiency virus type 1(HIV-1) coreceptor CCR5. It has in vitro activity against R5 viruses with 50% inhibitory concentrations ranging from 1.0 to 30.9 nM. We have studied anti-HIV-1 interactions of SCH-C with other antiretroviral agents in vitro. Synergistic interactions were seen with nucleoside reverse transcriptase inhibit...

Enveloped viruses that rely on a low pH-dependent step for entry initiate infection by fusing with acidic endosomes, whereas the entry sites for pH-independent viruses, such as HIV-1, have not been defined. These viruses have long been assumed to fuse directly with the plasma membrane. Here we used population-based measurements of the viral content delivery into the cytosol and time-resolved im...

OBJECTIVE T20 (Enfuvirtide), which is a 36-residue peptide derived from the C-terminal heptad repeat (CHR) of gp41, is the only clinically available HIV-1 fusion inhibitor, but it easily induces drug resistance, which calls for next-generation drugs. DESIGN We recently demonstrated that the M-T hook structure can be used to design a short CHR peptide that specifically targets the conserved gp...