Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes
Kirsten White, Nathan Osman, Ernesto Cuadra-Foy, Bluma Brenner, Devleena Shivakumar, Federico Campigotto, Manuel Tsiang, Philip Morganelli, Nikolai Novikov, Scott E. Lazerwith, Haolun Jin, Anita Niedziela‐Majka
Abstract
and maintained longer antiviral activity after drug washout than DTG with the clinically relevant resistance IN mutant G140S+Q148H. Structural analyses indicate that BIC makes more contacts with the IN-DNA complex than DTG mainly via its bicyclic ring system which may contribute to more prolonged residence time and resilience against many resistance mutations.
Topics & Concepts
ElvitegravirDolutegravirIntegraseRaltegravirMutantChemistryVirologyIntegrase inhibitorDNAStereochemistryPharmacologyBiologyHuman immunodeficiency virus (HIV)Viral loadBiochemistryAntiretroviral therapyGeneHIV/AIDS drug development and treatmentBiochemical and Molecular ResearchHIV Research and Treatment