RT info:eu-repo/semantics/article
T1 The Lupane-type Triterpene 30-Oxo-calenduladiol Is a CCR5 Antagonist with Anti-HIV-1 and Anti-chemotactic Activities.
A1 Valenzuela Fernández, Agustín
A1 Barroso Gonzá´lez, Jonathan
A1 El Jaber-Vazdekis, Nabil
A1 García Expoósito, Laura
A1 Machado, José David
A1 Zárate, Rafael
A1 Ravelo, Ángel G.
A1 Estévez-Braun, Ana
A2 Medicina Física y Farmacología
A2 Grupo "Inmunología Celular y Viral".
AB The existence of drug-resistant human immunodeficiencyvirus (HIV) viruses in patients receiving antiretroviral treatmenturgently requires the characterization and development of newantiretroviral drugs designed to inhibit resistant viruses and tocomplement the existing antiretroviral strategies against AIDS.We assayed several natural or semi-synthetic lupane-type pentacyclic triterpenes in their ability to inhibit HIV-1 infection inpermissive cells. We observed that the 30-oxo-calenduladioltriterpene, compound 1, specifically impaired R5-tropic HIV-1envelope-mediated viral infection and cell fusion in permissivecells, without affecting X4-tropic virus. This lupane derivativecompeted for the binding of a specific anti-CCR5 monoclonalantibody or the natural CCL5 chemokine to the CCR5 viral coreceptor with high affinity. 30-Oxo-calenduladiol seems not tointeract with the CD4 antigen, the main HIV receptor, or theCXCR4 viral coreceptor. Our results suggest that compound 1 isa specific CCR5 antagonist, because it binds to the CCR5 receptor without triggering cell signaling or receptor internalization,and inhibits RANTES (regulated on activation normal T cellexpressed and secreted)-mediated CCR5 internalization, intracellular calcium mobilization, and cell chemotaxis. Furthermore, compound 1 appeared not to interact with !-chemokinereceptors CCR1, CCR2b, CCR3, or CCR4. Thereby, the 30-oxocalenduladiol-associated anti-HIV-1 activity against R5-tropicvirus appears to rely on the selective occupancy of the CCR5 receptor to inhibit CCR5-mediated HIV-1 infection. Therefore,it is plausible that the chemical structure of 30-oxo-calenduladiol or other related dihydroxylated lupane-type triterpenescould represent a good model to develop more potent antiHIV-1 molecules to inhibit viral infection by interfering withearly fusion and entry steps in the HIV life cycle.
YR 2009
FD 2009
LK http://riull.ull.es/xmlui/handle/915/35341
UL http://riull.ull.es/xmlui/handle/915/35341
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 19-nov-2024