ArticleAntimicrobial agents and chemotherapy2011
Potent strategy to inhibit HIV-1 by binding both gp120 and gp41.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- The Antiviral Potential of Algal Lectins.Marine drugs · 2023Review
- Sustained Delivery of the Antiviral Protein Griffithsin and Its Adhesion to a Biological Surface by a Silk Fibroin Scaffold.Materials (Basel, Switzerland) · 2023Article
- A bivalent protein targeting glycans and HR1 domain in spike protein potently inhibited infection of SARS-CoV-2 and other human coronaviruses.Cell & bioscience · 2021Article
- Synergistic Effect by Combining a gp120-Binding Protein and a gp41-Binding Antibody to Inactivate HIV-1 Virions and Inhibit HIV-1 Infection.Molecules (Basel, Switzerland) · 2021Article
- Griffithsin, a Highly Potent Broad-Spectrum Antiviral Lectin from Red Algae: From Discovery to Clinical Application.Marine drugs · 2019Review
- Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41.Viruses · 2019Review
- Design of Poly(lactic-Pharmaceutics · 2019Article
- HIV Entry and Its Inhibition by Bifunctional Antiviral Proteins.Molecular therapy. Nucleic acids · 2018Review
- Pharmaceutical Approaches to HIV Treatment and Prevention.Advanced therapeutics · 2018Article
- Bifunctional Chimera That Coordinately Targets Human Immunodeficiency Virus 1 Envelope gp120 and the Host-Cell CCR5 Coreceptor at the Virus-Cell Interface.Journal of medicinal chemistry · 2018Article
- The Effect of N-Terminal Cyclization on the Function of the HIV Entry Inhibitor 5P12-RANTES.International journal of molecular sciences · 2017Article
- Stabilization and Sustained Release of HIV Inhibitors by Encapsulation in Silk Fibroin Disks.ACS biomaterials science & engineering · 2017Article
- Enhanced potency of bivalent small molecule gp41 inhibitors.Bioorganic & medicinal chemistry · 2017Article
- Article
- Review
- Structure-activity relationship studies of indole-based compounds as small molecule HIV-1 fusion inhibitors targeting glycoprotein 41.Journal of medicinal chemistry · 2014Article
- A novel gene therapy strategy using secreted multifunctional anti-HIV proteins to confer protection to gene-modified and unmodified target cells.Gene therapy · 2014Article
- Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.Antimicrobial agents and chemotherapy · 2014Article
- Chimeric Cyanovirin-MPER recombinantly engineered proteins cause cell-free virolysis of HIV-1.Antimicrobial agents and chemotherapy · 2013Article
- The role of individual carbohydrate-binding sites in the function of the potent anti-HIV lectin griffithsin.Molecular pharmaceutics · 2012Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The development of an anti-HIV microbicide is critical in the fight against the spread of HIV. It is shown here that the covalent linking of compounds that bind gp120 with compounds that bind gp41 can inhibit HIV entry even more potently than individual inhibitors or noncovalent combinations. The most striking example involves griffithsin, a potent HIV inhibitor that binds to the surface of HIV gp120. While griffithsin inhibits HIV Env-mediated fusion in a CCR5-tropic cell-cell fusion assay with a 50% inhibitory concentration (IC(50)) of 1.31 ± 0.87 nM and the gp41-binding peptide C37 shows an IC(50) of 18.2 ± 7.6 nM, the covalently linked combination of griffithsin with C37 (Griff37) has an IC(50) of 0.15 ± 0.05 nM, exhibiting a potency 8.7-fold greater than that of griffithsin alone. Similarly, in CXCR4-tropic cell-cell fusion assays, Griff37 is 5.2-fold more potent than griffithsin alone. In viral assays, both griffithsin and Griff37 inhibit HIV replication at midpicomolar levels, but the linked compound Griff37 is severalfold more potent than griffithsin alone against both CCR5- and CXCR4-tropic virus strains. Another example of this strategy is the covalently linked combination of peptide C37 with a variant of the gp120-binding peptide CD4M33 (L. Martin et al., Nat. Biotechnol. 21:71-76, 2003). Also, nuclear magnetic resonance (NMR) spectra for several of these compounds are shown, including, to our knowledge, the first published NMR spectrum for griffithsin.
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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.