ChemInform Abstract: Synthesis and Antiviral Activity of Cyclopropyl-Spirocarbocyclic Adenosine, (4R,5S,6R,7R)-4-(6-Amino-9H-purin-9-yl)-7-(hydroxymethyl)spiro [2.4]heptane-5,6-diol Against Hepatitis C Virus.

ChemInform ◽  
2011 ◽  
Vol 42 (47) ◽  
pp. no-no
Author(s):  
Srinivas Gadthula ◽  
Ravindra K. Rawal ◽  
Ashoke Sharon ◽  
Dong Wu ◽  
Brent Korba ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity

scholarly journals Iron Regulator Hepcidin Exhibits Antiviral Activity against Hepatitis C Virus

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e46631 ◽  
Author(s):  
Hongyan Liu ◽  
Thu Le Trinh ◽  
Huijia Dong ◽  
Robertson Keith ◽  
David Nelson ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity

scholarly journals Impaired antiviral activity of interferon alpha against hepatitis C virus 2a in Huh-7 cells with a defective Jak-Stat pathway

2010 ◽  
Vol 7 (1) ◽  
pp. 36 ◽  
Author(s):  
Sidhartha Hazari ◽  
Partha K Chandra ◽  
Bret Poat ◽  
Sibnarayan Datta ◽  
Robert F Garry ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Interferon Alpha ◽  
Stat Pathway

scholarly journals Short-Term Monotherapy with IDX184, a Liver-Targeted Nucleotide Polymerase Inhibitor, in Patients with Chronic Hepatitis C Virus Infection

2012 ◽  
Vol 56 (12) ◽  
pp. 6372-6378 ◽  
Author(s):  
Jacob Lalezari ◽  
David Asmuth ◽  
Arnaldo Casiró ◽  
Hugo Vargas ◽  
Shannon Lawrence ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Adverse Events ◽  
Antiviral Activity ◽  
Chronic Hepatitis C ◽  
Hcv Rna ◽  
Plasma Exposure ◽  
Chronic Hepatitis C Virus

ABSTRACTIDX184 is a liver-targeted prodrug of 2′-methylguanosine (2′-MeG) monophosphate. This study investigated the safety, tolerability, antiviral activity, and pharmacokinetics of IDX184 as a single agent in treatment-naïve patients with genotype-1 chronic hepatitis C virus (HCV) infection. Forty-one patients with baseline HCV RNA ≥ 5 log10IU/ml, alanine aminotransferase (ALT) ≤ 2.5× the upper limit of normal, and compensated liver disease were dosed. Sequential cohorts of 10 patients, randomized 8:2 (active:placebo), received 25, 50, 75, and 100 mg of IDX184 once daily for 3 days, with a 14-day follow-up. There were no safety-related treatment discontinuations or serious adverse events. The adverse events and laboratory abnormalities observed for IDX184- and placebo-treated patients were similar. At the end of the 3-day treatment period, changes from baseline in HCV RNA levels (means ± standard deviations) were −0.5 ± 0.6, −0.7 ± 0.2, −0.6 ± 0.3, and −0.7 ± 0.5 log10for the 25-, 50-, 75-, and 100-mg doses, respectively, while viral load remained unchanged for the pooled placebo patients (−0.05 ± 0.3 log10). Patients with genotype-1a and patients with genotype-1b responded similarly. Serum ALT levels decreased, especially at daily doses ≥ 75 mg. During the posttreatment period, plasma viremia and serum aminotransferase levels returned to near pretreatment levels. No resistance mutations associated with IDX184 were detected. Plasma exposure of IDX184 and its nucleoside metabolite 2′-MeG was dose related and low. Changes in plasma viral load correlated with plasma exposure of 2′-MeG. In conclusion, the results from this proof-of-concept study show that small doses of the liver-targeted prodrug IDX184 were able to deliver significant antiviral activity and support further clinical evaluation of the drug candidate.

The Safety and Antiviral Activity of BZF961 with or without Ritonavir in Patients Infected with Hepatitis C Virus: A Randomized, Multicenter Trial

2018 ◽  
Vol 40 (9) ◽  
pp. 1567-1581.e4
Author(s):  
Eric Lawitz ◽  
Mohamed Bidair ◽  
Thomas Marbury ◽  
Christopher T. Jones ◽  
Avantika Barve ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Multicenter Trial

Modeling the antiviral activity of ribavirin against hepatitis C virus in cell culture

Hepatology ◽  
2013 ◽  
Vol 58 (4) ◽  
pp. 1203-1206
Author(s):  
Daniel J. Felmlee ◽  
Fei Xiao ◽  
Thomas F. Baumert
Keyword(s):  
Cell Culture ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity

ChemInform Abstract: A Facile Synthesis of (5-Hydroxy-4-oxo-4H-pyran-2-yl)methyl Carboxylates and Their Antiviral Activity Against Hepatitis C Virus.

ChemInform ◽  
2013 ◽  
Vol 44 (39) ◽  
pp. no-no
Author(s):  
Tetsuro Shimo ◽  
Yuki Taketsugu ◽  
Takuya Goto ◽  
Masaaki Toyama ◽  
Kohji Yoshimura ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Facile Synthesis

scholarly journals Comparison of Daclatasvir Resistance Barriers on NS5A from Hepatitis C Virus Genotypes 1 to 6: Implications for Cross-Genotype Activity

2014 ◽  
Vol 58 (9) ◽  
pp. 5155-5163 ◽  
Author(s):  
Chunfu Wang ◽  
Lingling Jia ◽  
Donald R. O'Boyle ◽  
Jin-Hua Sun ◽  
Karen Rigat ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Rank Order ◽  
Replicon Cell ◽  
Hcv Genotypes ◽  
Resistance Selection ◽  
Virus Genotypes ◽  
Hepatitis C Virus Genotypes

ABSTRACTA comparison of the daclatasvir (DCV [BMS-790052]) resistance barrier on authentic or hybrid replicons containing NS5A from hepatitis C virus (HCV) genotypes 1 to 6 (GT-1 to -6) was completed using a replicon elimination assay. The data indicated that genotype 1b (GT-1b) has the highest relative resistance barrier and genotype 2a (GT-2a M31) has the lowest. The rank order of resistance barriers to DCV was 1b > 4a ≥ 5a > 6a ≅ 1a > 2a JFH > 3a > 2a M31. Importantly, DCV in combination with a protease inhibitor (PI) eliminated GT-2a M31 replicon RNA at a clinically relevant concentration. Previously, we reported the antiviral activity and resistance profiles of DCV on HCV genotypes 1 to 4 evaluated in the replicon system. Here, we report the antiviral activity and resistance profiles of DCV against hybrid replicons with NS5A sequences derived from HCV GT-5a and GT-6a clinical isolates. DCV was effective against both GT-5a and -6a hybrid replicon cell lines (50% effective concentrations [EC50s] ranging from 3 to 7 pM for GT-5a, and 74 pM for GT-6a). Resistance selection identified amino acid substitutions in the N-terminal domain of NS5A. For GT-5a, L31F and L31V, alone or in combination with K56R, were the major resistance variants (EC50s ranging from 2 to 40 nM). In GT-6a, Q24H, L31M, P32L/S, and T58A/S were identified as resistance variants (EC50s ranging from 2 to 250 nM). Thein vitrodata suggest that DCV has the potential to be an effective agent for HCV genotypes 1 to 6 when used in combination therapy.

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