title: HIV-1 resistance mechanism to an electrostatically constrained peptide fusion inhibitor that is active against T-20-resistant strains.
abstract: T-20EK is a novel fusion inhibitor designed to have enhanced α-helicity over T-20 (enfuvirtide) through engineered electrostatic interactions between glutamic acid (E) and lysine (K) substitutions. T-20EK efficiently suppresses wild-type and T-20-resistant variants. Here, we selected T-20EK-resistant variants. A combination of L33S and N43K substitutions in gp41 were required for high resistance to T-20EK. While these substitutions also caused resistance to T-20, they did not cause cross-resistance to other known fusion inhibitors.
authors.affiliation: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Shimane
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawaji
authors.forename: Fusako
authors.initials: F
authors.lastname: Miyamoto
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Sakagami
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimura
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kaku
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Sarafianos
authors.forename: Eiichi N
authors.initials: EN
authors.lastname: Kodama
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D045744:Cell Line, Tumor; D024882:Drug Resistance, Viral; D000077560:Enfuvirtide; D018698:Glutamic Acid / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D055672:Static Electricity
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide; D018698:Glutamic Acid; D008239:Lysine