A new adaptive L1-norm for optimal descriptor selection of high-dimensional QSAR classification model for anti-hepatitis C virus activity of thiourea derivatives

2017 ◽  
Vol 28 (1) ◽  
pp. 75-90 ◽  
Author(s):  
Z. Y. Algamal ◽  
M. H. Lee
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Classification Model ◽  
High Dimensional ◽  
L1 Norm ◽  
Thiourea Derivatives ◽  
Virus Activity ◽  
Descriptor Selection ◽  
Optimal Descriptor ◽  
Selection Of

scholarly journals Characterization of Resistance to the Nonnucleoside NS5B Inhibitor Filibuvir in Hepatitis C Virus-Infected Patients

2011 ◽  
Vol 56 (3) ◽  
pp. 1331-1341 ◽  
Author(s):  
Philip J. F. Troke ◽  
Marilyn Lewis ◽  
Paul Simpson ◽  
Katrina Gore ◽  
Jennifer Hammond ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Site Directed Mutagenesis ◽  
Phenotypic Resistance ◽  
Number Of Patients ◽  
Chronic Hcv ◽  
Selection Of

ABSTRACTFilibuvir (PF-00868554) is an investigational nonnucleoside inhibitor of the hepatitis C virus (HCV) nonstructural 5B (NS5B) RNA-dependent RNA polymerase currently in development for treating chronic HCV infection. The aim of this study was to characterize the selection of filibuvir-resistant variants in HCV-infected individuals receiving filibuvir as short (3- to 10-day) monotherapy. We identified amino acid M423 as the primary site of mutation arising upon filibuvir dosing. Through bulk cloning of clinical NS5B sequences into a transient-replicon system, and supported by site-directed mutagenesis of the Con1 replicon, we confirmed that mutations M423I/T/V mediate phenotypic resistance. Selection in patients of an NS5B mutation at M423 was associated with a reduced replicative capacityin vitrorelative to the pretherapy sequence; consistent with this, reversion to wild-type M423 was observed in the majority of patients following therapy cessation. Mutations at NS5B residues R422 and M426 were detected in a small number of patients at baseline or the end of therapy and also mediate reductions in filibuvir susceptibility, suggesting these are rare but clinically relevant alternative resistance pathways. Amino acid variants at position M423 in HCV NS5B polymerase are the preferred pathway for selection of viral resistance to filibuvirin vivo.

scholarly journals High-dimensional immune phenotyping of blood cells by mass cytometry in patients infected with hepatitis C virus

2021 ◽  
Author(s):  
Jacobus Herderschee ◽  
Tytti Heinonen ◽  
Craig Fenwick ◽  
Irene T. Schrijver ◽  
Khalid Ohmiti ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Blood Cells ◽  
High Dimensional ◽  
Mass Cytometry ◽  
Immune Phenotyping

scholarly journals Statins potentiate thein vitroanti-hepatitis C virus activity of selective hepatitis C virus inhibitors and delay or prevent resistance development

Hepatology ◽  
2009 ◽  
Vol 50 (1) ◽  
pp. 6-16 ◽  
Author(s):  
Leen Delang ◽  
Jan Paeshuyse ◽  
Inge Vliegen ◽  
Pieter Leyssen ◽  
Susan Obeid ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Resistance Development ◽  
Virus Activity

Winners of the Nobel Prize in Medicine in 2020

2021 ◽  
pp. 59-63
Author(s):  
Oksana Aleksandrovna Rybachok
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nobel Prize ◽  
The Body ◽  
Coronavirus Infection ◽  
First Time ◽  
Selection Of

Despite the height of the coronavirus infection, the Nobel Prize in Medicine was awarded in Stockholm in October 2020. This event was held online for the first time and was not accompanied by the traditional honoring of the laureates. In his will, Alfred Nobel entrusted the selection of the winner in this nomination to the Karolinska Medical and Surgical University of Stockholm, and the first award in this nomination took place in 1901. Since then, this event has been held 110 times, and 216 scientists have become laureates of the prize in the field of physiology and medicine, since the nominees are often not just one, but a group of researchers. This happened in 2020 - for research in the field of studying the hepatitis C virus, three scientists received the most prestigious award: the British Michael Houghton and the Americans Harvey Alter and Charles Rice. Due to the results of the research, which these three people conducted separately from each other, for the first time it became possible to completely eliminate the virus from the body.

scholarly journals Anti-HIV and Anti-Hepatitis C Virus Drugs Inhibit P-Glycoprotein Efflux Activity in Caco-2 Cells and Precision-Cut Rat and Human Intestinal Slices

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Ondrej Martinec ◽  
Martin Huliciak ◽  
Frantisek Staud ◽  
Filip Cecka ◽  
Ivan Vokral ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Molecular Mechanisms ◽  
Interindividual Variability ◽  
Ex Vivo ◽  
Efflux Transporter ◽  
P Glycoprotein ◽  
Bidirectional Transport ◽  
Anti Hiv ◽  
Selection Of

ABSTRACT P-glycoprotein (ABCB1), an ATP-binding-cassette efflux transporter, limits intestinal absorption of its substrates and is a common site of drug-drug interactions (DDIs). ABCB1 has been suggested to interact with many antivirals used to treat HIV and/or chronic hepatitis C virus (HCV) infections. Using bidirectional transport experiments in Caco-2 cells and a recently established ex vivo model of accumulation in precision-cut intestinal slices (PCIS) prepared from rat ileum or human jejunum, we evaluated the potential of anti-HIV and anti-HCV antivirals to inhibit intestinal ABCB1. Lopinavir, ritonavir, saquinavir, atazanavir, maraviroc, ledipasvir, and daclatasvir inhibited the efflux of a model ABCB1 substrate, rhodamine 123 (RHD123), in Caco-2 cells and rat-derived PCIS. Lopinavir, ritonavir, saquinavir, and atazanavir also significantly inhibited RHD123 efflux in human-derived PCIS, while possible interindividual variability was observed in the inhibition of intestinal ABCB1 by maraviroc, ledipasvir, and daclatasvir. Abacavir, zidovudine, tenofovir disoproxil fumarate, etravirine, and rilpivirine did not inhibit intestinal ABCB1. In conclusion, using recently established ex vivo methods for measuring drug accumulation in rat- and human-derived PCIS, we have demonstrated that some antivirals have a high potential for DDIs on intestinal ABCB1. Our data help clarify the molecular mechanisms responsible for reported increases in the bioavailability of ABCB1 substrates, including antivirals and drugs prescribed to treat comorbidity. These results could help guide the selection of combination pharmacotherapies and/or suitable dosing schemes for patients infected with HIV and/or HCV.

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