ArticlePLoS pathogens2019
Monotherapy with a low-dose lipopeptide HIV fusion inhibitor maintains long-term viral suppression in rhesus macaques.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 47 citations in OpenAlex.
- Phosphorylation of shiftless is important for inhibiting the programmed -1 ribosomal frameshift.Science advances · 2025Article
- The pathogenicity and multi-organ proteomic profiles of Mpox virus infection in SIVmac239-infected rhesus macaques.Nature communications · 2025Article
- Addition of a short HIV-1 fusion-inhibitory peptide to PRO 140 antibody dramatically increases its antiviral breadth and potency.Journal of virology · 2025Article
- A penta-component mpox mRNA vaccine induces protective immunity in nonhuman primates.Nature communications · 2024Article
- Article
- IgG Fc-Binding Peptide-Conjugated Pan-CoV Fusion Inhibitor Exhibits Extended In Vivo Half-Life and Synergistic Antiviral Effect When Combined with Neutralizing Antibodies.Biomolecules · 2023Article
- TLR7 Agonist GS-9620 Combined with Nicotinamide Generate Viral Reactivation in Seronegative SHIVBiomedicines · 2023Article
- Design and characterization of novel SARS-CoV-2 fusion inhibitors with N-terminally extended HR2 peptides.Antiviral research · 2023Article
- SARS-CoV-2 fusion-inhibitory lipopeptides maintain high potency against divergent variants of concern including Omicron.Emerging microbes & infections · 2022Article
- Potent inhibition of diverse Omicron sublineages by SARS-CoV-2 fusion-inhibitory lipopeptides.Antiviral research · 2022Article
- Recent advances in developing small-molecule inhibitors against SARS-CoV-2.Acta pharmaceutica Sinica. B · 2022Review
- A Modified Fibronectin Type III Domain-Conjugated, Long-Acting Pan-Coronavirus Fusion Inhibitor with Extended Half-Life.Viruses · 2022Article
- Peptide-Based HIV Entry Inhibitors.Advances in experimental medicine and biology · 2022Article
- Structure-based design and characterization of novel fusion-inhibitory lipopeptides against SARS-CoV-2 and emerging variants.Emerging microbes & infections · 2021Article
- Peptide Amphiphilic-Based Supramolecular Structures with Anti-HIV-1 Activity.Bioconjugate chemistry · 2021Article
- Novel Antiretroviral Therapeutic Strategies for HIV.Molecules (Basel, Switzerland) · 2021Review
- Therapeutic targets and interventional strategies in COVID-19: mechanisms and clinical studies.Signal transduction and targeted therapy · 2021Review
- Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy.Signal transduction and targeted therapy · 2021Review
- Generation of HIV-resistant cells with a single-domain antibody: implications for HIV-1 gene therapy.Cellular & molecular immunology · 2021Article
- Stage-Dependent Within-Individual Comparison Reveals SIV-Specific Activation/Exhaustion Shift in Rhesus Macaques.Frontiers in microbiology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Combination antiretroviral therapy (cART) dramatically improves survival of HIV-infected patients, but lifelong treatment can ultimately result in cumulative toxicities and drug resistance, thus necessitating the development of new drugs with significantly improved pharmaceutical profiles. We recently found that the fusion inhibitor T-20 (enfuvirtide)-based lipopeptides possess dramatically increased anti-HIV activity. Herein, a group of novel lipopeptides were designed with different lengths of fatty acids, identifying a stearic acid-modified lipopeptide (LP-80) with the most potent anti-HIV activity. It inhibited a large panel of divergent HIV subtypes with a mean IC50 in the extremely low picomolar range, being > 5,300-fold more active than T-20 and the neutralizing antibody VRC01. It also sustained the potent activity against T-20-resistant mutants and exhibited very high therapeutic selectivity index. Pharmacokinetics of LP-80 in rats and monkeys verified its potent and long-acting anti-HIV activity. In the monkey, subcutaneous administration of 3 mg/kg LP-80 yielded serum concentrations of 1,147 ng/ml after injection 72 h and 9 ng/ml after injection 168 h (7 days), equivalent to 42,062- and 330-fold higher than the measured IC50 value. In SHIV infected rhesus macaques, a single low-dose LP-80 (3 mg/kg) sharply reduced viral loads to below the limitation of detection, and twice-weekly monotherapy could maintain long-term viral suppression.
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