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| Emergence of drug resistant HIV-1 mutants is a serious problem for AIDS treatment. SC29EK, a shorter variant of SC34EK, is one of the representative next-generation fusion inhibitors of HIV-1. It shows high activity on inhibiting both wide type and T-20 resistant HIV-1 strains. In this study, we focused on the selection and characterization of HIV-1 escape mutants of SC29EK. Three mutations, Q39R, N43K and E49A located at N-heptad repeat regions and N126K located at C-heptad repeat region of gp41 were identified. High resistance to pocket targeting inhibitor peptides and cross-resistance to enfuvirtide (T20) and sifuvirtide (SFT) were detected, with the mechanisms of significantly reducing binding affinity of the inhibitors and dramatically enhancing interaction of the viral six-helix bundle. Our data helps increase the understanding of the structure-function relationship of gp41 and HIV-1 evolution, providing a reference for the clinical application of fusion inhibitors.????? |
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| Keywords:HIV-1; fusion inhibitor; resistance |
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