S
Samir Ali
Researcher at Hoffmann-La Roche
Publications - 10
Citations - 715
Samir Ali is an academic researcher from Hoffmann-La Roche. The author has contributed to research in topics: Hepatitis C virus & Replicon. The author has an hindex of 6, co-authored 10 publications receiving 698 citations.
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Journal ArticleDOI
The Hepatitis C Virus Replicon Presents a Higher Barrier to Resistance to Nucleoside Analogs than to Nonnucleoside Polymerase or Protease Inhibitors
Matthew F. McCown,Sonal Rajyaguru,Sophie Le Pogam,Samir Ali,Wen-Rong Jiang,Hyunsoon Kang,Julian Symons,Nick Cammack,Isabel Najera +8 more
TL;DR: Results indicate that the HCV replicon presents a higher barrier to the selection of resistance to nucleoside inhibitors than to nonnucleoside or protease inhibitors, which could have a clear clinical benefit through the delay of resistance emergence.
Journal ArticleDOI
Selection and Characterization of Replicon Variants Dually Resistant to Thumb- and Palm-Binding Nonnucleoside Polymerase Inhibitors of the Hepatitis C Virus
Sophie Le Pogam,Hyunsoon Kang,Seth F. Harris,Vincent Leveque,Anthony M. Giannetti,Samir Ali,Wen-Rong Jiang,Sonal Rajyaguru,Gisele A. Tavares,Connie Oshiro,Than Hendricks,Klaus Klumpp,Julian Symons,Michelle F. Browner,Nick Cammack,Isabel Najera +15 more
TL;DR: These findings demonstrate the selection of replicon variants dually resistant to two NS5B polymerase inhibitors binding to different sites of the enzyme, and provide initial insights into the in vitro mutational threshold of the HCV NS5 B polymerase and the potential impact of viral fitness on theselection of multiple-resistant mutants.
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In vitro selected Con1 subgenomic replicons resistant to 2'-C-methyl-cytidine or to R1479 show lack of cross resistance.
Sophie Le Pogam,Wen-Rong Jiang,Vincent Leveque,Sonal Rajyaguru,Han Ma,Hyunsoon Kang,Sharon Jiang,Margaret Singer,Samir Ali,Klaus Klumpp,Dave Smith,Julian Symons,Nick Cammack,Isabel Najera +13 more
TL;DR: The characterization of the inhibitory effect of 2'-C-Methyl-Cytidine shows that it is a potent inhibitor of both genotype 1b and 1a HCV replicon replication, both of laboratory-optimized as well as of NS5B clinical isolates-chimera replicons.
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Characterization of the Metabolic Activation of Hepatitis C Virus Nucleoside Inhibitor β-d-2′-Deoxy-2′-fluoro-2′-C-methylcytidine (PSI-6130) and Identification of a Novel Active 5′-Triphosphate Species
Han Ma,Wen-Rong Jiang,Nicole Robledo,Vincent Leveque,Samir Ali,Teresa Lara-Jaime,Mohammad R. Masjedizadeh,David Bernard Smith,Nick Cammack,Klaus Klumpp,Julian Symons +10 more
TL;DR: It is demonstrated that PSI-6130 is metabolized to two pharmacologically active species in primary human hepatocytes through the formation of 5′-triphosphate and its corresponding phosphorylated metabolites.
Journal ArticleDOI
Selected Replicon Variants with Low-Level In Vitro Resistance to the Hepatitis C Virus NS5B Polymerase Inhibitor PSI-6130 Lack Cross-Resistance with R1479
Samir Ali,Vincent Leveque,Sophie Le Pogam,Han Ma,Friederike Philipp,Nicole Inocencio,Mark D. Smith,André Alker,Hyunsoon Kang,Isabel Najera,Klaus Klumpp,Julian Symons,Nick Cammack,Wen-Rong Jiang +13 more
TL;DR: PSI-6130 presents a high barrier to resistance selection in vitro, selects for variants exhibiting only low-level resistance, and lacks cross-resistance with R1479, supporting the continued development of the prodrug R7128 as a therapeutic agent for the treatment of HCV infection.