The DOI matches its Crossref record; the references it cites are not checked yet.
Viral Entry as the Primary Target for the Anti-HIV Activity of Chicoric Acid and Its Tetra-Acetyl Esters
Abstract
The antiviral activity of L-chicoric acid against HIV-1 has been attributed previously to the inhibition of HIV-1 integration. This conclusion was based on the inhibition of integrase activity in enzymatic assays and the isolation of a resistant HIV strain with a mutation (G140S) in the integrase gene. Here we show that the primary antiviral target of L-CA and its analogs in cell culture is viral entry. L- and D-chicoric acid (L-CA and D-CA) and their respective tetra-acetyl esters inhibit the replication of HIV-1 (III(B) and NL4.3) and HIV-2 (ROD) in MT-4 cells at a 50% effective concentration (EC(50)) ranging from 1.7 to 70.6 microM. In a time-of-addition experiment, L-CA, D-CA, L-CATA, and D-CATA were found to interfere with an early event in the viral replication cycle. Moreover, L-CA, D-CA, and their analogs did not inhibit the replication of virus strains that were resistant toward polyanionic and polycationic compounds at subtoxic concentrations. Furthermore, HIV-1 strains resistant to L-CA and D-CA were selected in the presence of L-CA and D-CA, respectively. Mutations were found in the V2, V3, and V4 loop region of the envelope glycoprotein gp120 of the L-CA and D-CA-resistant NL4.3 strains that were not present in the wild-type NL4.3 strain. Recombination of the gp120 gene of the L-CA and D-CA resistant strain in a NL4.3 wild-type molecular clone fully rescued the phenotypic resistance toward L-CA and D-CA. No significant mutations were detected in the integrase gene of the drug-resistant virus strains. Although inhibition of HIV integrase activity by L-CA and its derivatives was confirmed in an oligonucleotide-driven assay, integrase carrying the G140S mutation was inhibited to the same extent as the wild-type integrase.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
The citation lists haven’t been fetched yet
References 46 · Cited by 111
Research works printed but not linked: 41
- Adachi, 1986, Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone., J Virol, 59, 284, 10.1128/JVI.59.2.284-291.1986 · DOI
- 10.1126/science.6189183 · DOI · Paper page
- Bonn, 1998, Green coffee beans may yield new class of anti-HIV-1 agents., Lancet, 352, 1039, 10.1016/S0140-6736(05)60082-7 · DOI
- 10.1021/jm00002a019 · DOI
- Brown, 1997, Integration of retroviral DNA., Curr Topics Microbiol Immunol, 157, 19
- 10.1124/mol.52.5.771 · DOI
- 10.1096/fj.14.10.1389 · DOI
- 10.1099/0022-1317-68-12-3183 · DOI
- De Vreese, 1996, The molecular target of bicyclams, potent inhibitors of human immunodeficiency virus replication., J Virol, 70, 689, 10.1128/JVI.70.2.689-696.1996 · DOI
- Debyser Z Cherepanov P Pluymers W De Clercq E (2000) Assays for the Evaluation of HIV-1 Integrase Inhibitors. in Methods in Molecular Biology. Nuclease Methods and Protocols, ed Schein CH (The Humana Press, Inc. Totowa, NJ) , in press.
- 10.1124/mol.53.2.340 · DOI
- 10.1124/mol.52.1.98 · DOI
- 10.1056/NEJM199709113371101 · DOI
- 10.1038/9886 · DOI
- 10.1126/science.2992081 · DOI
- 10.1126/science.287.5453.646 · DOI · Paper page
- 10.1021/jo01030a546 · DOI · Paper page
- 10.1128/AAC.37.5.1095 · DOI
- 10.1074/jbc.271.13.7712 · DOI
- 10.1021/jm9804735 · DOI
- King, 1998, Resistance to the anti-human immunodeficiency virus type 1 compound l-chicoric acid results from a single mutation at amino acid 140 of integrase., J Virol, 72, 8420, 10.1128/JVI.72.10.8420-8424.1998 · DOI
- 10.1021/jm980531m · DOI
- 10.1177/095632029300400406 · DOI · Paper page
- Mazumder A Neamati N Sunder S Owen J Pommier Y (1999) Retroviral integrase: A novel target in antiviral development. Basic in vitro assays with the purified enzyme. in Antiviral Methods and Protocols, eds Kinchington D Schinazi R (The Humana Press, Inc, Totowa, NJ), pp 327–335. · DOI
- McDougall, 1998, Dicaffeoylquinic and dicaffeoyltartaric acids are selective inhibitors of human immunodeficiency virus type 1 integrase., Antimicrob Agents Chemother, 42, 140, 10.1128/AAC.42.1.140 · DOI · Paper page
- 10.1016/S1359-6446(97)01105-7 · DOI
- 10.1038/343470a0 · DOI
- 10.1016/0166-0934(88)90134-6 · DOI
- Pommier, 1997, HIV-1 integrase as a target for antiviral drugs., Antimicrob Agents Chemother, 8, 463
- 10.1126/science.6200935 · DOI
- 10.1074/jbc.270.4.1754 · DOI
- 10.1016/S0166-3542(98)00037-0 · DOI
- Robinson, 1996, Dicaffeoylquinic acid inhibitors of human immunodeficiency virus integrase: Inhibition of the core catalytic domain of human immunodeficiency virus integrase., Mol Pharmacol, 50, 846, 10.1016/S0026-895X(25)09385-X · DOI
- 10.1073/pnas.93.13.6326 · DOI
- Schinazi, 1996, Mutations in retroviral genes associated with drug resistance., Int Antivir News, 4, 95
- Schols, 1998, T-cell-line-tropic human immunodeficiency virus type 1 that is made resistant to stromal cell-derived factor 1α contains mutations in the envelope gp120 but does not show a switch in coreceptor use., J Virol, 72, 4032, 10.1128/JVI.72.5.4032-4037.1998 · DOI
- 10.1084/jem.186.8.1383 · DOI
- 10.1016/S0167-7799(97)01016-0 · DOI
- 10.1016/0031-9422(95)00865-9 · DOI
- Zhao, 1998, Facile syntheses of (2R,3R)-(−)- and (2S,3S)-(+)-chicoric acids., Synth Commun, 28, 737, 10.1080/00397919808005946 · DOI
- Zhu, 1999, Irreversible inhibition of human immunodeficiency virus type 1 integrase by dicaffeoylquinic acids., J Virol, 73, 3309, 10.1128/JVI.73.4.3309-3316.1999 · DOI
Metadata
- Authors
- Pluymers, W., Neamati, N., Pannecouque, C., Fikkert, V., Marchand, C., Burke, T. R., Pommier, Y., Schols, D., De Clercq, E., Debyser, Z., & Witvrouw, M.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 2000-09-01
- Volume
- 58
- Issue
- 3
- Pages
- 641-648
- ISSN
- 0026-895X (ISSN-L)
- 1521-0111
- OpenAlex
- W1851303894
- Cited by
- 111
- References
- 46
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 1 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 7.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- chicoric acid, HIV-1, HIV-2, viral entry inhibition, antiviral activity, drug resistance, HIV-1 replication, MT-4 cells
- MeSH terms
- Caffeic Acids, Cells, Cultured, Escherichia coli, Humans, Leukocytes, Mononuclear, Recombinant Proteins, Succinates, Time Factors, Virus Replication, HIV-1, HIV Envelope Protein gp120, Mutagenesis, Site-Directed, Anti-HIV Agents, HIV Integrase, Integrase Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
