ArticleThe Journal of biological chemistry2019
HIV-1 anchor inhibitors and membrane fusion inhibitors target distinct but overlapping steps in virus entry.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Current ARTs, Virologic Failure, and Implications for AIDS Management: A Systematic Review.Viruses · 2023Pooled it
- Pharmacokinetic-pharmacodynamic modeling of a highly potent and broadly neutralizing anti-CD4 trimeric nanobody to inhibit HIV-1 infection.Microbiology spectrum · 2025Article
- Natural Compounds with Antiviral Activity Against Clinically Relevant RNA Viruses: Advances of the Last Decade.Biomolecules · 2025Review
- Macropinosomes are a site of HIV-1 entry into primary CD4Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Antiretroviral Therapy in Pregnancy: A 2023 Review of the Literature.Current HIV/AIDS reports · 2024Review
- SARS-CoV-2 Fusion Peptide Conjugated to a Tetravalent Dendrimer Selectively Inhibits Viral Infection.Pharmaceutics · 2023Article
- Broad-Spectrum Antivirals Derived from Natural Products.Viruses · 2023Review
- Design of hACE2-based small peptide inhibitors against spike protein of SARS-CoV-2: a computational approach.Structural chemistry · 2023Article
- Article
- Identification of antiviral peptide inhibitors for receptor binding domain of SARS-CoV-2 omicron and its sub-variants: an in-silico approach.3 Biotech · 2022Article
- In Vitro Selection and Characterization of HIV-1 Variants with Increased Resistance to LP-40, Enfuvirtide-Based Lipopeptide Inhibitor.International journal of molecular sciences · 2022Article
- Conserved Targets to Prevent Emerging Coronaviruses.Viruses · 2022Review
- Comparative analysis of machine learning-based approaches for identifying therapeutic peptides targeting SARS-CoV-2.Briefings in bioinformatics · 2022Article
- Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms.International journal of molecular sciences · 2022Review
- The CCR5 Gene Edited CD34Frontiers in immunology · 2022Article
- Peptide-Based Vaccines and Therapeutics for COVID-19.International journal of peptide research and therapeutics · 2022Review
- Peptide and peptide-based inhibitors of SARS-CoV-2 entry.Advanced drug delivery reviews · 2020Review
- Identification of the natural product berberine as an antiviral drug.AMB Express · 2020Article
- Polyethylene Glycol 40-Modified Peptide with High Therapeutic Efficacy in Simian-Human Immunodeficiency Virus-Acutely Infected Rhesus Monkeys.Journal of virology · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
HIV-1 entry into cells is mediated by the envelope glycoprotein (Env) and represents an attractive target for therapeutic intervention. Two drugs that inhibit HIV entry are approved for clinical use: the membrane fusion-inhibitor T20 (Fuzeon, enfuvirtide) and the C-C chemokine receptor type 5 (CCR5) blocker maraviroc (Selzentry). Another class of entry inhibitors supposedly target the fusion peptide (FP) and are termed anchor inhibitors. These include the VIRIP peptide and VIRIP derivatives such as VIR165, VIR353, and VIR576. Here, we investigated the mechanism of inhibition by VIR165. We show that substitutions within the FP modulate sensitivity to VIR165, consistent with the FP being the drug target. Our results also revealed that VIR165 acts during an intermediate post-CD4-binding entry step that is overlapping but not identical to the step inhibited by fusion inhibitors such as T20. We found that some but not all resistance mutations to heptad repeat 2 (HR2)-targeting fusion inhibitors can provide cross-resistance to VIR165. In contrast, resistance mutations in the HR1-binding site for the fusion inhibitors did not cause cross-resistance to VIR165. However, Env with mutations located outside this binding site and thought to affect fusion kinetics, exhibited decreased sensitivity to VIR165. Although we found a strong correlation between Env stability and resistance to HR2-based fusion inhibitors, such correlation was not observed for Env stability and VIR165 resistance. We conclude that VIRIP analogs target the FP during an intermediate, post-CD4-binding entry step that overlaps with but is distinct from the step(s) inhibited by HR2-based fusion inhibitors.
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Registered trials
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.