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Virginie MORALES


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3 publication(s) depuis Juin 2001:

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Les IF indiqués ont été collectés par le Web of Sciences en

15/11/2015 | bioorg med chem lett   IF 2.4
Discovery and structural diversity of the hepatitis C virus NS3/4A serine protease inhibitor series leading to clinical candidate IDX320.
Parsy CC, Alexandre FR, Bidau V, Bonnaterre F, Brandt G, Caillet C, Cappelle S, Chaves D, Convard T, Derock M, Gloux D, Griffon Y, Lallos LB, Leroy F, Liuzzi M, Loi AG, Moulat L, Chiara M, Rahali H, Roques V, Rosinovsky E, Savin S, Seifer M, Standring D, Surleraux D

Exploration of the P2 region by mimicking the proline motif found in BILN2061 resulted in the discovery of two series of potent HCV NS3/4A protease inhibitors. X-ray crystal structure of the ligand in contact with the NS3/4A protein and modulation of the quinoline heterocyclic region by structure based design and modeling allowed for the optimization of enzyme potency and cellular activity. This research led to the selection of clinical candidate IDX320 having good genotype coverage and pharmacokinetic properties in various species.

14/09/2011 | EMBO J   IF 11.2
Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain.
Favereaux A*, Thoumine O.*, Bouali-Benazzouz*, Roques V, Papon M.A., Abdel Salam S., Drutel G., Leger C, Calas A., Nagy F.*, Landry M.*

Chronic pain states are characterized by long-term sensitization of spinal cord neurons that relay nociceptive information to the brain. Among the mechanisms involved, up-regulation of Cav1.2-comprising L-type calcium channel (Cav1.2-LTC) in spinal dorsal horn have a crucial role in chronic neuropathic pain. Here, we address a mechanism of translational regulation of this calcium channel. Translational regulation by microRNAs is a key factor in the expression and function of eukaryotic genomes. Because perfect matching to target sequence is not required for inhibition, theoretically, microRNAs could regulate simultaneously multiple mRNAs. We show here that a single microRNA, miR-103, simultaneously regulates the expression of the three subunits forming Cav1.2-LTC in a novel integrative regulation. This regulation is bidirectional since knocking-down or over-expressing miR-103, respectively, up- or down-regulate the level of Cav1.2-LTC translation. Functionally, we show that miR-103 knockdown in naive rats results in hypersensitivity to pain. Moreover, we demonstrate that miR-103 is down-regulated in neuropathic animals and that miR-103 intrathecal applications successfully relieve pain, identifying miR-103 as a novel possible therapeutic target in neuropathic chronic pain.

06/2001 | J Virol   IF 4.3
Immunoglobulin G (IgG) and IgA, but also nonantibody factors, account for in vitro neutralization of human immunodeficiency virus (HIV) type 1 primary isolates by serum and plasma of HIV-infected patients.
Burrer R, Salmon-Ceron D, Richert S, Pancino G, Spiridon G, Haessig S, Roques V, Barre-Sinoussi F, Aubertin AM, Moog C

The factors present in serum and plasma samples of human immunodeficiency virus (HIV)-infected patients that are responsible for the neutralization of four HIV type 1 (HIV-1) primary isolates in vitro have been analyzed. Purification of immunoglobulins (Ig) by affinity chromatography showed that the activities were mostly attributable to IgG and less frequently to IgA. For two samples, we have shown that the high-level and broad-spectrum inhibitory activity was essentially caused by non-Ig factors interfering with the measurement of antibody-specific neutralizing activity.