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Feglymycin (FGM), a natural Streptomyces-derived 13mer peptide, consistently inhibits HIV replication in the lower μM range. FGM also inhibits HIV cell-to-cell transfer between HIV-infected T cells and uninfected CD4 + T cells and the DC-SIGN-mediated viral transfer to CD4 + T cells. FGM potently interacts with gp120 (X4 and R5) as determined by SPR analysis and shown to act as a gp120/CD4...
Raltegravir is the first integrase strand-transfer inhibitor (INSTI) approved for use in highly active antiretroviral therapy (HAART) for the management of HIV infection. Resistance to antiretrovirals can compromise the efficacy of HAART regimens. Therefore it is important to understand the emergence of resistance to RAL and cross-resistance to other INSTIs including potential second-generation INSTIs...
Emergence of resistance to raltegravir reduces its treatment efficacy in HIV-1-infected patients. To delineate the effect of resistance mutations on viral susceptibility to integrase inhibitors, in vitro resistance selections with raltegravir and with MK-2048, an integrase inhibitor with a second-generation-like resistance profile, were performed. Mutation Q148R arose in four out of six raltegravir-selected...
The 2G12 mAb inhibits the infection of HIV-1 laboratory-adapted viruses at 50% inhibitory concentrations (IC 50 ) ranging from 0.02 to 0.2 μg/ml when evaluated in different cell-types. However, isolates from various HIV-1 subtypes (such as clade C, D, A/E, F and group O) were not inhibited by 2G12 mAb (IC 50 >20 μg/ml). 2G12 mAb pressure in HIV-1 IIIB- and NL4.3-infected T cell...
The interaction of the CXCR4 antagonist AMD3100 with its target is greatly influenced by specific aspartate residues in the receptor protein, including Asp 171 and Asp 262 . We have now found that aspartate-to-asparagine substitutions at these positions differentially affect the binding of four different anti-CXCR4 monoclonal antibodies as well as the infectivity...
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