title: Inhibition of DC-SIGN-mediated HIV infection by a linear trimannoside mimic in a tetravalent presentation.
abstract: HIV infection is pandemic in humans and is responsible for millions of deaths every year. The discovery of new cellular targets that can be used to prevent the infection process represents a new opportunity for developing more effective antiviral drugs. In this context, dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN), a lectin expressed at the surface of immature dendritic cells and involved in the initial stages of HIV infection, is a promising therapeutic target. Herein we show the ability of a new tetravalent dendron containing four copies of a linear trimannoside mimic to inhibit the trans HIV infection process of CD4+ T lymphocytes at low micromolar range. This compound presents a high solubility in physiological media, a neglectable cytotoxicity, and a long-lasting effect and is based on carbohydrate-mimic units. Notably, the HIV antiviral activity is independent of viral tropism (X4 or R5). The formulation of this compound as a gel could allow its use as topical microbicide.
authors.affiliation: Dipartimento di Chimica Organica e Industriale and CISI, Universita degli Studi di Milano, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Sattin
authors.forename: Anna
authors.initials: A
authors.lastname: Daghetti
authors.forename: Michel
authors.initials: M
authors.lastname: Thépaut
authors.forename: Angela
authors.initials: A
authors.lastname: Berzi
authors.forename: Macarena
authors.initials: M
authors.lastname: Sánchez-Navarro
authors.forename: Georges
authors.initials: G
authors.lastname: Tabarani
authors.forename: Javier
authors.initials: J
authors.lastname: Rojo
authors.forename: Franck
authors.initials: F
authors.lastname: Fieschi
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
authors.forename: Anna
authors.initials: A
authors.lastname: Bernardi
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D002240:Carbohydrate Sequence; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008362:Mannosides / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020349:Surface Plasmon Resonance; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D019380:Anti-HIV Agents; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008362:Mannosides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin