Format

Send to

Choose Destination
PLoS One. 2016 Oct 27;11(10):e0165386. doi: 10.1371/journal.pone.0165386. eCollection 2016.

A Cinnamon-Derived Procyanidin Compound Displays Anti-HIV-1 Activity by Blocking Heparan Sulfate- and Co-Receptor- Binding Sites on gp120 and Reverses T Cell Exhaustion via Impeding Tim-3 and PD-1 Upregulation.

Author information

1
Institut de Biologie Structurale, UMR 5075, Univ. Grenoble Alpes, CNRS, CEA, F-38027 Grenoble, France.
2
School of Medical Technology, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan.
3
Indus Biotech Pvt Ltd, Pune, India.
4
Laboratoire de Neurovirologie, Bertin Pharma, CEA, 92265 Fontenay aux Roses, France.
5
Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria.
6
INSERM U1110, Fédération de médecine translationnelle de Strasbourg (FMTS), Institut de Virologie, 3 rue Koeberlé, 67000 Strasbourg, France.
7
Division of Emerging Infectious Diseases, Miyagi Communitiy Health Promotion, Tohoku University School of Medicine, Bldg. 1, Rm. 515, 2-1 Seiryocho, Aoba-ku, Sendai 980-8575, Japan.

Abstract

Amongst the many strategies aiming at inhibiting HIV-1 infection, blocking viral entry has been recently recognized as a very promising approach. Using diverse in vitro models and a broad range of HIV-1 primary patient isolates, we report here that IND02, a type A procyanidin polyphenol extracted from cinnamon, that features trimeric and pentameric forms displays an anti-HIV-1 activity against CXCR4 and CCR5 viruses with 1-7 μM ED50 for the trimer. Competition experiments, using a surface plasmon resonance-based binding assay, revealed that IND02 inhibited envelope binding to CD4 and heparan sulphate (HS) as well as to an antibody (mAb 17b) directed against the gp120 co-receptor binding site with an IC50 in the low μM range. IND02 has thus the remarkable property of simultaneously blocking gp120 binding to its major host cell surface counterparts. Additionally, the IND02-trimer impeded up-regulation of the inhibitory receptors Tim-3 and PD-1 on CD4+ and CD8+ cells, thereby demonstrating its beneficial effect by limiting T cell exhaustion. Among naturally derived products significantly inhibiting HIV-1, the IND02-trimer is the first component demonstrating an entry inhibition property through binding to the viral envelope glycoprotein. These data suggest that cinnamon, a widely consumed spice, could represent a novel and promising candidate for a cost-effective, natural entry inhibitor for HIV-1 which can also down-modulate T cell exhaustion markers Tim-3 and PD-1.

PMID:
27788205
PMCID:
PMC5082894
DOI:
10.1371/journal.pone.0165386
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: Drs Ekambaranellore Prakash and Viswaraman Mohan are employees of Indus Biotech, which provided the IND-02 compound and supported this work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center