title: 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.
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.
authors: Institut de Biologie Structurale, UMR 5075, Univ. Grenoble Alpes, CNRS, CEA, F-38027 Grenoble, France.
authors: Bridgette Janine
authors: BJ
authors: Connell
authors: School of Medical Technology, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Sui-Yuan
authors: SY
authors: Chang
authors: Indus Biotech Pvt Ltd, Pune, India.
authors: Ekambaranellore
authors: E
authors: Prakash
authors: Laboratoire de Neurovirologie, Bertin Pharma, CEA, 92265 Fontenay aux Roses, France.
authors: Rahima
authors: R
authors: Yousfi
authors: Indus Biotech Pvt Ltd, Pune, India.
authors: Viswaraman
authors: V
authors: Mohan
authors: Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria.
authors: Wilfried
authors: W
authors: Posch
authors: Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria.
authors: Doris
authors: D
authors: Wilflingseder
authors: INSERM U1110, Fédération de médecine translationnelle de Strasbourg (FMTS), Institut de Virologie, 3 rue Koeberlé, 67000 Strasbourg, France.
authors: Christiane
authors: C
authors: Moog
authors: 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.
authors: Eiichi N
authors: EN
authors: Kodama
authors: Laboratoire de Neurovirologie, Bertin Pharma, CEA, 92265 Fontenay aux Roses, France.
authors: Pascal
authors: P
authors: Clayette
authors: Institut de Biologie Structurale, UMR 5075, Univ. Grenoble Alpes, CNRS, CEA, F-38027 Grenoble, France.
authors: Hugues
authors: H
authors: Lortat-Jacob
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D044946:Biflavonoids / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology*; D002935:Cinnamomum zeylanicum / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000378:metabolism*; D006801:Humans; D044945:Proanthocyanidins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D044946:Biflavonoids; D015704:CD4 Antigens; D002392:Catechin; D015699:HIV Envelope Protein gp120; D006497:Heparan Sulfate; D000072597:Hepatitis A Virus Cellular Receptor 2; D044945:Proanthocyanidins; D061026:Programmed Cell Death 1 Receptor; C448908:HAVCR2 protein, human; C000607183:IND02 polymer; C105992:PDCD1 protein, human; C017674:procyanidin