Rapid clinical progress of hepatitis C virus (HCV) replication inhibitors, including these selecting for resistance in the NS5A region (NS5A inhibitors), promises to revolutionize HCV treatment. Herein, we describe our explorations of diverse spiropyrrolidine motifs in novel NS5A inhibitors and a proposed interaction model. We discovered that the 1,4-dioxa-7-azaspiro[4.4]nonane motif in inhibitor 41H (GSK2236805) supported high potency against genotypes 1a and 1b as well as in genotype 1b L31V and Y93H mutants. Consistent with this, 41H potently suppressed HCV RNA in the 20-day RNA reduction assay. Pharmacokinetic and safety data supported further progression of 41H to the clinic.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm4013104 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Diagnosis and therapy of chronic hepatitis D: Czech national guideline].
Klin Mikrobiol Infekc Lek
September 2023
Infectious Disease Clinic Faculty of Medicine and University Hospital Brno; Czech Repubic, e-mail:
For the first time, a separate Czech guideline focuses exclusively on hepatitis D virus (HDV) infection. Until recently, HDV infection was only mentioned in guidelines concerning hepatitis B virus (HBV) infection, in chapters on HBV/HDV co-infection. The guideline is based on the July 2023 recommendations from the European Association for the Study of the Liver.
View Article and Find Full Text PDFHepatitis B vaccine and juvenile idiopathic arthritis: comparison of the seropositivity rates with healthy children at the time of diagnosis and booster dose response under treatment.
Clin Rheumatol
January 2025
Department of Pediatric Rheumatology, Zeynep Kamil Women and Children's Diseases Training and Research Hospital, Istanbul, Turkey.
Introduction/objectives: The study aimed to determine whether in children with newly diagnosed juvenile idiopathic arthritis (JIA) hepatitis B surface antibody (anti-HBs) differs from healthy children and to see whether the revaccination is safe and effective under JIA treatment.
Methods: Patients who were followed up with a diagnosis of JIA between January 2020 and February 2024 were included. The control group consisted of healthy children matched for age and gender.
Background: Hepatitis C virus (HCV) and hepatitis B virus (HBV) infections pose significant global health concerns, contributing to chronic liver diseases. Blood transfusion is identified as a potential route for the transmission of these viruses, necessitating effective screening strategies for blood donors. The aim of this study was to assess the significance of nucleic acid testing (NAT) in detecting HBV and HCV infections among blood donors who initially tested negative in serological tests.
View Article and Find Full Text PDFNew recommendations of Spanish Society of Emergency Medicine (SEMES) for emergency department diagnosis of HIV infection based on results from Spain's "Leave Your Mark" program.
Emergencias
December 2024
Servicio de Urgencias, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, España.
Hidden infections and late diagnoses are currently the main challenges of the HIV pandemic. Emergency departments (EDs) are one of the health care system's key resources addressing these challenges. In 2020, the Spanish Society of Emergency Medicine (SEMES) published recommendations for ordering HIV serology testing for patients with certain health conditions, and in 2021 SEMES launched the "Leave Your Mark" (Deja tu Huella - DTH) program to facilitate implementing the recommendations during emergency care.
View Article and Find Full Text PDFQuantitative Analysis of Hepatitis D Virus Using gRNA-Sensitive Semiconducting Polymer Dots.
Anal Chem
January 2025
State Key Laboratory of Integrated Optoelectronics, College of Electronics Science and Engineering, Jilin University, No. 2699 Qianjin Street, Changchun, Jilin 130012, P. R. China.
Hepatitis D virus (HDV) significantly influences the progression of liver diseases. Through clinical observations and database analyses, it has been established that patients coinfected with HDV and hepatitis B virus (HBV) experience accelerated progression toward cirrhosis, hepatocellular carcinoma (HCC), and liver failure compared to those infected solely with HBV. A higher viral load correlates with increased replicative activity, enhanced infectivity, and more severe disease manifestations.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!