Direct acting antiviral agents to cure hepatitis C virus (HCV) infection has emerged as the gold standard therapy. Along with protease inhibitors, nucleoside polymerase inhibitors and non-nucleoside polymerase inhibitors, the inhibition of NS5a has proved to be an effective way to treat HCV patients. Here we report on novel HCV NS5a inhibitors which were synthesized and evaluated in the HCV replicon assay. A series of inhibitors were formed by a cycloaddition reaction in parallel to establish new leads and explore the effects of unsymmetrical cap substitution. This led to the identification of several triazoles with picomolar potency in vitro against hepatitis C virus.
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http://dx.doi.org/10.1007/s11030-017-9733-z | DOI Listing |
J Mol Graph Model
December 2024
Faculty of Chemistry and Center for Computational Science, Hanoi National University of Education, Hanoi, Viet Nam; Institute of Natural Sciences, Hanoi National University of Education, Hanoi, Viet Nam.
The Hepatitis C virus (HCV) causes a variety of liver diseases, making it a global health issue that affects millions of people in the world. The NS3/4A protease has been considered a common target for anti-HCV treatments using direct-acting antiviral agents and their derivatives. Of the natural products that have been proposed for novel therapeutic product alternatives, the soft coral compounds are found to contain steroids with various bioactive properties for effective HCV treatments.
View Article and Find Full Text PDFViruses
November 2024
Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro 21040-361, RJ, Brazil.
Coronavirus disease 2019 (COVID-19) still causes death in elderly and immunocompromised individuals, for whom the sustainability of the vaccine response may be limited. Antiviral treatments, such as remdesivir or molnupiravir, have demonstrated limited clinical efficacy. Nirmatrelvir, an acute respiratory syndrome coronavirus 2 (SARS-CoV-2) major protease inhibitor, is clinically effective but has been associated with viral rebound and antiviral resistance.
View Article and Find Full Text PDFACS Omega
December 2024
College of Science and Engineering, Hamad Bin Khalifa University, Doha 34110, Qatar.
Sci Rep
December 2024
Bioinformatics Laboratory, College of Computing, University Mohammed VI Polytechnic, Ben Guerir, Morocco.
Hepatitis C virus (HCV) presents a significant global health issue due to its widespread prevalence and the absence of a reliable vaccine for prevention. While significant progress has been achieved in therapeutic interventions since the disease was first identified, its resurgence underscores the need for innovative strategies to combat it. The nonstructural protein NS5A is crucial in the life cycle of the HCV, serving as a significant factor in both viral replication and assembly processes.
View Article and Find Full Text PDFComput Biol Med
December 2024
KAM School of Life Sciences, Forman Christian College University, Lahore, Pakistan. Electronic address:
Classification of viruses carries important implications in terms of understanding their evolution and the designing of interventions. This study introduces ViroNia as a novel LSTM-based system specifically meant for high-accuracy classification of viral proteins. Although originally developed for generative tasks, LSTM architectures have been found to be highly efficient for classification tasks as well; the model demonstrates this capability.
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