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Article

Kinetic Investigation of Resistance to Islatravir Conferred by Mutations in HIV-1 Reverse Transcriptase.

Journal of molecular biology - 15 Jun 2025

Zalenski Nikita, Meredith Brianna R, Savoie Derek J, Naas Mohamed J, Suo David J, Betancourt Daniel, Seay Turner W, Suo Zucai

Abstract excerpt

Islatravir (EFdA) is a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI) that potently blocks HIV-1 replication in vivo. Its unique structural features in contrast to nucleoside reverse transcriptase inhibitors (NRTIs), particularly the 4'-ethynyl and 3'-hydroxy groups, contribute to its high clinical potency. Once intracellularly activated to EFdA 5'-triphosphate (EFdA-TP), it competes with...

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Identifiers

PMID: 40139311
DOI: 10.1016/j.jmb.2025.169100

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Kinetic Investigation of Resistance to Islatravir Conferred by Mutations in HIV-1 Reverse Transcriptase.PMID 40139311Read ↗

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Islatravir Has a High Barrier to Resistance and Exhibits a Differentiated Resistance Profile from Approved Nucleoside Reverse Transcriptase Inhibitors (NRTIs).Semantic proximity Read ↗

Structural and Mechanistic Basis of F227C-Mediated Hypersusceptibility to Islatravir in HIV-1 Reverse TranscriptaseSemantic proximity Read ↗

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HIV-1 Resistance to Islatravir/Tenofovir Combination Therapy in Wild-Type or NRTI-Resistant Strains of Diverse HIV-1 Subtypes.Semantic proximity Read ↗

HIV-1 resistance to islatravir/tenofovir combination therapy in wild-type or NRTI resistant strains of diverse HIV-1 subtypesSemantic proximity Read ↗

Development of Resistance to 4’-Ethynyl-2-Fluoro-2’-Deoxyadenosine (EFdA) by WT and Nucleoside Reverse Transcriptase Inhibitor Resistant Human Immunodeficiency Virus Type 1Semantic proximity Read ↗

Variable antiviral activity of islatravir against M184I/V mutant HIV-1 selected during antiretroviral therapy.Semantic proximity Read ↗

M184V: The Major Determinant of Cooperative ISL Resistance When in Combination with Multiple TAM2 Mutations in HIV-1 Subtype CSemantic proximity Read ↗

Doravirine and Islatravir Have Complementary Resistance Profiles and Create a Combination with a High Barrier to Resistance.Semantic proximity Read ↗

Unraveling the Mechanism of HIV-1 Hypersusceptibility to Tenofovir Imparted by Islatravir Resistance MutationsSemantic proximity Read ↗

No antagonism or cross-resistance and a high barrier to the emergence of resistance in vitro for the combination of islatravir and lenacapavir.Semantic proximity Read ↗

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