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Abstract Background and Aim The efficacy and safety profiles of elbasvir–grazoprevir (EBR/GZR) has been established in more than 10 clinical trials. However, the characteristics of patients treated in routine clinical practice may differ. The present study was therefore designed to assess the real‐life effectiveness of EBR/GZR therapy in the general population and among subgroups with a high hepatitis C virus (HCV) prevalence in France. Methods The Zephyr study was designed as a French, multicentre, prospective, observational study on EBR/GZR use and effectiveness in current practice in chronic hepatitis C patients. These results are based on data regarding the adult patients who received at least one dose of EBR/GZR between December 2017 and June 2019 in 67 French hospitals and clinics. Results Overall, 478 patients were included. The Full Analysis Set corresponded to the 467 patients who met all the inclusion criteria and none of the exclusion criteria. Gender was balanced and the mean age was 55.7 ± 13.3 years. The patients were mainly treatment‐naive (89.5%) and infected with Genotype 1b (70.4%). Among the 75 patients with HCV Gt1a genotype, 56% had HCV RNA ≥ 800,000 IU/ml. F3–F4 fibrosis stage involved 24.2% of our population. Our subgroups were distributed among 110 migrants (23.6%), 58 (15.3%) using opioid agonist treatment, including people who inject drugs, 30 (6.8%) with chronic kidney disease Stages 3–5, 9 (1.9%) with an inherited blood disorder, and 4 (0.9%) coinfected with HIV. The remaining 269 (58.7%) were included in the general population subgroup. Overall, sustained virologic response 12 weeks after the end of treatment reached 98.0% and remained consistent among genotype, HCV RNA values, fibrosis stage, and the subgroup of interest. The rate of Alcohol Use Disorders Identification Test‐Consumption​​​ and Life Habit questionnaire completion was high at each visit, with data suggesting alcohol consumption decrease and an improvement in quality of life. Conclusions Using real‐world evidence data on a French population representative of HCV patients, we confirmed the results obtained during EBR/GZR development program.

Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket properties for ligand binding.