Nonnucleoside Reverse Transcriptase Inhibitor Hypersusceptibility and Resistance by Mutation of Residue 181 in HIV-1 Reverse Transcriptase.
Alkynes
Anti-HIV Agents
/ pharmacology
Benzoxazines
/ pharmacology
Cyclopropanes
Drug Resistance, Viral
/ genetics
Fluorescence Polarization
HIV Reverse Transcriptase
/ genetics
HIV-1
/ drug effects
Humans
Mutation
/ genetics
Nevirapine
/ pharmacology
Reverse Transcriptase Inhibitors
/ pharmacology
Rilpivirine
/ pharmacology
HIV
NNRTI
mechanisms of resistance
reverse transcriptase
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
29
03
2019
accepted:
27
05
2019
pubmed:
5
6
2019
medline:
9
6
2020
entrez:
5
6
2019
Statut:
epublish
Résumé
Substitutions at residue Y181 in HIV-1 reverse transcriptase (RT), in particular, Y181C, Y181I, and Y181V, are associated with nonnucleoside RT inhibitor (NNRTI) cross-resistance. In this study, we used kinetic and thermodynamic approaches, in addition to molecular modeling, to gain insight into the mechanisms by which these substitutions confer resistance to nevirapine (NVP), efavirenz (EFV), and rilpivirine (RPV). Using pre-steady-state kinetics, we found that the dissociation constant (
Identifiants
pubmed: 31160281
pii: AAC.00676-19
doi: 10.1128/AAC.00676-19
pmc: PMC6658764
pii:
doi:
Substances chimiques
Alkynes
0
Anti-HIV Agents
0
Benzoxazines
0
Cyclopropanes
0
Reverse Transcriptase Inhibitors
0
Nevirapine
99DK7FVK1H
reverse transcriptase, Human immunodeficiency virus 1
EC 2.7.7.-
HIV Reverse Transcriptase
EC 2.7.7.49
Rilpivirine
FI96A8X663
efavirenz
JE6H2O27P8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI081571
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM068406
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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