A5051540586- Hepatitis C virus research
- Cardiac Arrest and Resuscitation
- Hepatitis B Virus Studies
- HIV/AIDS drug development and treatment
- Trauma and Emergency Care Studies
- Non-Invasive Vital Sign Monitoring
- Liver Disease Diagnosis and Treatment
- Emergency and Acute Care Studies
- Pediatric Pain Management Techniques
- Biochemical and Molecular Research
- Musculoskeletal pain and rehabilitation
- Injury Epidemiology and Prevention
- Traumatic Brain Injury and Neurovascular Disturbances
- Opioid Use Disorder Treatment
- Monoclonal and Polyclonal Antibodies Research
- Mechanical Circulatory Support Devices
- Neurosurgical Procedures and Complications
- Quinazolinone synthesis and applications
- Healthcare Technology and Patient Monitoring
- Simulation-Based Education in Healthcare
- Clinical Laboratory Practices and Quality Control
- Infection Control and Ventilation
- COVID-19 and healthcare impacts
- Noise Effects and Management
- Traumatic Brain Injury Research
Centre Intégré Universitaire de Santé et de Services Sociaux du Centre-Sud-de-l'Île-de-Montréal
2018-2023
Hôpital du Sacré-Cœur de Montréal
2015-2023
Centre intégré universitaire de santé et de services sociaux du Nord-de-l’Île-de-Montréal
2020-2023
Université de Montréal
1998-2022
Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean
2022
Boehringer Ingelheim (Canada)
2004-2016
Boehringer Ingelheim (Germany)
2005
The virally encoded NS5B RNA-dependent RNA polymerase has emerged as a prime target in the search for specific HCV antivirals. A series of benzimidazole 5-carboxamide compounds inhibit cellular replication subgenomic replicon and we have advanced our understanding this class inhibitors through combination complementary approaches that include biochemical cross-linking experiments with photoreactive analogue followed by mass spectrometry analysis enzyme. novel binding site been localized...
BackgroundBILB 1941 is a potent and specific non-nucleoside inhibitor of the hepatitis C virus (HCV) RNA polymerase in vitro.MethodsIn double-blind sequential group comparison, 96 male HCV genotype 1 patients with minimal to mild liver fibrosis (Ishak or Metavir score 0–2) were randomized (8 active treatment 2 placebo per dose group) treated 10–450 mg BILB every 8 h over 5 days. Viral load (VL) was measured using Roche Cobas TaqMan® assays.ResultsVL decreased by ≥1 log10 IU/ml 2/8, 1/8, 2/7,...
A previously disclosed series of non-nucleoside allosteric inhibitors the NS5B polymerase hepatitis C virus (HCV) was optimized to yield novel compounds with improved physicochemical properties and activity in cell-based assays. Replacement ionizable carboxylic acids neutral substituents lead produced cellular permeability antiviral a assay subgenomic HCV RNA replication (replicon EC(50) as low 1.7 microM). The improvement potency this ex vivo model validates, part, mechanism by which class...
Natriuretic peptide receptor-A (NPR-A), a particulate guanylyl cyclase receptor, is composed of an extracellular domain (ECD) with ligand binding site, transmembrane spanning, kinase homology (KHD), and domain. Atrial natriuretic (ANP) brain (BNP), the natural agonists, bind activate receptor leading to cyclic GMP production. This has been reported be spontaneously dimeric or oligomeric. In response KHD-mediated guanylate repression removed, it assumed that ATP binds KHD. Since NPR-A...
The in vitro resistance profile of BI 201335 was evaluated through selection and characterization variants genotype 1a (GT 1a) 1b 1b) replicons. NS3 R155K D168V were the most frequently observed resistant variants. Phenotypic mutants revealed shifts sensitivity specific to that did not alter susceptibility alpha interferon. In contrast macrocyclic covalent protease inhibitors, changes at V36, T54, F43, Q80 confer 201335.
A challenge to the treatment of chronic hepatitis C with direct-acting antivirals is emergence drug-resistant virus (HCV) variants. HCV preexisting polymorphisms that are associated resistance NS3/4A protease inhibitors have been detected in patients C. We performed a comprehensive pooled analysis from phase 1b and 2 clinical studies inhibitor faldaprevir assess population frequency baseline resistance-associated NS3 their impact on response treatment. total 980 sequences were obtained (543...
The design and preliminary SAR of a new series 1H-quinazolin-4-one (QAZ) allosteric HCV NS5B thumb pocket 2 (TP-2) inhibitors was recently reported. To support optimization efforts, molecular dynamics (MD) based modeling workflow implemented, providing information on QAZ binding interactions with NS5B. This approach predicted small but critical ligand-binding induced movement protein backbone region which increases the size improves access to carbonyl groups Val 494 Pro 495. localized shift...
Deleobuvir (BI 207127) is an investigational oral nonnucleoside inhibitor of hepatitis C virus (HCV) NS5B RNA polymerase. Antiviral activity, virology, pharmacokinetics, and safety were assessed in HCV genotype 1-infected patients receiving 5 days' deleobuvir monotherapy. In this double-blind phase 1b study, treatment-naive (TN; n = 15) treatment-experienced (TE; 45) without cirrhosis received placebo or at 100, 200, 400, 800, 1,200 mg every 8 h (q8h) for days. Patients with (n 13) 400 600...
ABSTRACT Faldaprevir (BI 201335) is a selective NS3/4A protease inhibitor under development for the treatment of chronic hepatitis C virus (HCV) infection. genotyping and NS3 phenotyping analyses were performed to monitor emergence resistance in patients with HCV genotype 1 infection receiving faldaprevir alone or combined pegylated interferon alfa 2a ribavirin (PegIFN-RBV) during phase 1b study. Among all baseline variants, maximum 7-fold reduction vitro sensitivity was observed rare...
Percentage of pain intensity difference (PercentPID) is a recognized way evaluating relief with an 11-point numerical rating scale (NRS) but not without flaws. A new metric, the slope relative (SlopePID), which consists in dividing PercentPID by time between 2 measurements, proposed. This study aims to validate SlopePID 3 measures subjective relief: 5-category (not, little, moderate, very, complete), 2-category question ("I'm relieved," "I'm relieved"), and single-item question, "Wanting...
The development of interferon-free regimens for the treatment chronic HCV infection constitutes a preferred option that is expected in future to provide patients with improved efficacy, better tolerability, and reduced risk emergence drug-resistant virus. We have pursued non-nucleoside NS5B polymerase allosteric inhibitors as combination partners other direct acting antivirals (DAAs) having complementary mechanism action. Herein, we describe discovery potent follow-up compound (BI 207524,...
Abstract Background Emergency departments (EDs) are operating at or above capacity, which has negative consequences on patients in terms of quality care and morbi-mortality. Redirection strategies for low-acuity ED to primary practices usually based subjective eligibility criteria that sometimes necessitate formal medical assessment. Literature investigating the effect those interventions is equivocal. The aim present study was assess safety a redirection process using an electronic clinical...