ArticleRetrovirology2012
A bivalent recombinant protein inactivates HIV-1 by targeting the gp41 prehairpin fusion intermediate induced by CD4 D1D2 domains.
Article in Retrovirology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 64 citations in OpenAlex.
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- Characterization and Promising in vitro Antiherpetic Effect of Galactomannan from Delonix regia Seeds.Current microbiology · 2024Article
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- Alpaca-derived nanobody targeting the hydrophobic pocket of the HIV-1 gp41 NHR broadly neutralizes HIV-1 by blocking six-helix bundle formation.Current research in microbial sciences · 2024Article
- Extracellular domain, hinge, and transmembrane determinants affecting surface CD4 expression of a novel anti-HIV chimeric antigen receptor (CAR) construct.bioRxiv : the preprint server for biology · 2023Article
- A gossypol derivative effectively protects against Zika and dengue virus infection without toxicity.BMC biology · 2022Article
- A Protein-Based, Long-Acting HIV-1 Fusion Inhibitor with an Improved Pharmacokinetic Profile.Pharmaceuticals (Basel, Switzerland) · 2022Article
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- Virus Entry Inhibitors: Past, Present, and Future.Advances in experimental medicine and biology · 2022Review
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- 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
- Rational Design of A Novel Small-Molecule HIV-1 Inactivator Targeting Both gp120 and gp41 of HIV-1.Frontiers in pharmacology · 2020Article
- Protein- and Peptide-Based Virus Inactivators: Inactivating Viruses Before Their Entry Into Cells.Frontiers in microbiology · 2020Review
- IgG Fc-binding motif-conjugated HIV-1 fusion inhibitor exhibits improved potency and in vivo half-life: Potential application in combination with broad neutralizing antibodies.PLoS pathogens · 2019Article
- Erythromycin Estolate Inhibits Zika Virus Infection by Blocking Viral Entry as a Viral Inactivator.Viruses · 2019Article
- Identification of Novel Natural Products as Effective and Broad-Spectrum Anti-Zika Virus Inhibitors.Viruses · 2019Article
- Trimeric heptad repeat synthetic peptides HR1 and HR2 efficiently inhibit HIV-1 entry.Bioscience reports · 2019Article
- Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41.Viruses · 2019Review
- Design and Characterization of Cholesterylated Peptide HIV-1/2 Fusion Inhibitors with Extremely Potent and Long-Lasting Antiviral Activity.Journal of virology · 2019Article
- HIV Entry and Its Inhibition by Bifunctional Antiviral Proteins.Molecular therapy. Nucleic acids · 2018Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMost currently approved anti-HIV drugs (e.g., reverse transcriptase inhibitors, protease inhibitors and fusion/entry inhibitors) must act inside or on surface of the target cell to inhibit HIV infection, but none can directly inactivate virions away from cells. Although soluble CD4 (sCD4) can inactivate laboratory-adapted HIV-1 strains, it fails to reduce the viral loads in clinical trials because of its low potency against primary isolates and tendency to enhance HIV-1 infection at low concentration. Thus, it is essential to design a better HIV inactivator with improved potency for developing new anti-HIV therapeutics that can actively attack the virus in the circulation before it attaches to and enter into the target cell.
resultsWe engineered a bivalent HIV-1 inactivator, designated 2DLT, by linking the D1D2 domain of CD4 to T1144, the next generation HIV fusion inhibitor, with a 35-mer linker. The D1D2 domain in this soluble 2DLT protein could bind to the CD4-binding site and induce the formation of the gp41 prehairpin fusion-intermediate (PFI), but showed no sCD4-mediated enhancement of HIV-1 infection. The T1144 domain in 2DLT then bound to the exposed PFI, resulting in rapid inactivation of HIV-1 virions in the absence of the target cell. Beside, 2DLT could also inhibit fusion of the virus with the target cell if the virion escapes the first attack of 2DLT.
conclusionThis bivalent molecule can serve as a dual barrier against HIV infection by first inactivating HIV-1 virions away from cells and then blocking HIV-1 entry on the target cell surface, indicating its potential for development as a new class of anti-HIV drug.
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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.