ArticleJournal of virology2011
Resistance of human immunodeficiency virus type 1 to a third-generation fusion inhibitor requires multiple mutations in gp41 and is accompanied by a dramatic loss of gp41 function.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- Different mechanisms for human rhinovirus survival in the presence of deleterious amino acid substitutions at virion protein-protein or RNA-protein interfaces.Journal of virology · 2026Article
- Structure-Guided Design of Peptide Inhibitors Targeting Class I Viral Fusion Proteins.Pathogens (Basel, Switzerland) · 2025Review
- Design of a highly potent bifunctional HIV-1 entry inhibitor targeting both gp120 and gp41.RSC medicinal chemistry · 2025Article
- Vaginal bacterium Prevotella timonensis turns protective Langerhans cells into HIV-1 reservoirs for virus dissemination.The EMBO journal · 2022Article
- Convergent HIV-1 Evolution upon Targeted Destabilization of the gp120-gp41 Interface.Journal of virology · 2021Article
- Identification of an Antiretroviral Small Molecule That Appears To Be a Host-Targeting Inhibitor of HIV-1 Assembly.Journal of virology · 2021Article
- Entry Inhibitors: Efficient Means to Block Viral Infection.The Journal of membrane biology · 2020Review
- Therapeutic Efficacy and Resistance Selection of a Lipopeptide Fusion Inhibitor in Simian Immunodeficiency Virus-Infected Rhesus Macaques.Journal of virology · 2020Article
- Structural and Functional Characterization of the Secondary Mutation N126K Selected by Various HIV-1 Fusion Inhibitors.Viruses · 2020Article
- Rational Design of A Novel Small-Molecule HIV-1 Inactivator Targeting Both gp120 and gp41 of HIV-1.Frontiers in pharmacology · 2020Article
- The Tryptophan-Rich Motif of HIV-1 gp41 Can Interact with the N-Terminal Deep Pocket Site: New Insights into the Structure and Function of gp41 and Its Inhibitors.Journal of virology · 2019Article
- Characterization of resistance to a potent D-peptide HIV entry inhibitor.Retrovirology · 2019Article
- Article
- HIV-1 anchor inhibitors and membrane fusion inhibitors target distinct but overlapping steps in virus entry.The Journal of biological chemistry · 2019Article
- A Peptide-Based HIV-1 Fusion Inhibitor with Two Tail-Anchors and Palmitic Acid Exhibits Substantially Improved In Vitro and Ex Vivo Anti-HIV-1 Activity and Prolonged In Vivo Half-Life.Molecules (Basel, Switzerland) · 2019Article
- Monotherapy with a low-dose lipopeptide HIV fusion inhibitor maintains long-term viral suppression in rhesus macaques.PLoS pathogens · 2019Article
- HIV Entry and Its Inhibition by Bifunctional Antiviral Proteins.Molecular therapy. Nucleic acids · 2018Review
- Reduced Susceptibility to VIRIP-Based HIV-1 Entry Inhibitors Has a High Genetic Barrier and Severe Fitness Costs.Journal of virology · 2018Article
- Molecular mechanism of HIV-1 resistance to sifuvirtide, a clinical trial-approved membrane fusion inhibitor.The Journal of biological chemistry · 2018Article
- HIV-1 gp41 Residues Modulate CD4-Induced Conformational Changes in the Envelope Glycoprotein and Evolution of a Relaxed Conformation of gp120.Journal of virology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIV-1 entry into target cells requires the fusion of viral and cellular membranes. This process is an attractive target for therapeutic intervention, and a first-generation fusion inhibitor, T20 (Enfuvirtide; Fuzeon), was approved for clinical use in 2003. Second-generation (T1249) and third-generation (T2635) fusion inhibitors with improved stability and potency were developed. Resistance to T20 and T1249 usually requires one or two amino acid changes within the binding site. We studied the in vitro evolution of resistance against T2635. After 6 months of culturing, a multitude of resistance mutations was identified in all gp41 subdomains, but no single mutation provided meaningful T2635 resistance. In contrast, multiple mutations within gp41 were required for resistance, and this was accompanied by a dramatic loss of viral infectivity. Because most of the escape mutations were situated outside the T2635 binding site, a decrease in drug target affinity cannot account for most of the resistance. T2635 resistance is likely to depend on altered kinetics of six-helix bundle formation, thus limiting the time window for T2635 to interfere with membrane fusion. Interestingly, the loss of virus infectivity caused by T2635 resistance mutations in gp41 was partially compensated for by a mutation at the base of the V3 domain in gp120. Thus, escape from the third-generation HIV-1 fusion inhibitor T2635 is mechanistically distinct from resistance against its predecessors T20 and T1249. It requires the accumulation of multiple mutations in gp41, is accompanied with a dramatic loss of gp41 function, and induces compensatory mutations in gp120.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.