scholarly journals Tyrosinase from mushroom Agaricus bisporus as an inhibitor of the Hepatitis C virus

2020 ◽  
Author(s):  
David Lopez-Tejedor ◽  
Rafael Clavería-Gimeno ◽  
Adrian Velazquez-Campoy ◽  
Olga Abian ◽  
Jose M. Palomo
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Agaricus Bisporus ◽  
Catalytic Mechanism ◽  
Low Cost ◽  
Inhibition Mechanism ◽  
System A ◽  
Viral Proteases ◽  
Hepatitis C Virus Proteins

AbstractTyrosinases from both a commercial semi-purified Agaricus bisporus protein extract and directly isolated from white mushroom have been demonstrated to show antiviral activity against the Hepatitis C virus for the first time. The well-known tyrosinase from A. bisporus (TyrAB) of 45kDa and a newly discovered 50-kDa isoform from this tyrosinase (Tyr50kDa) have been tested. Cell toxicity and antiviral activity of tyrosinases in cultured Huh 5-2 liver tumor cells transfected with a replicon system (a plasmid that includes all non-structural Hepatitis C virus proteins and replicates autonomously) was determined. Native TyrAB was able to inhibit the replication of the hepatitis C virus without inducing toxicity in liver cells. In addition, the post-translational isoform of Tyr50kDa showed higher antiviral capacity than the former (up to 10 times greater), , also exhibiting 10 times higher activity than the commercial drug Ribavirin®. This antiviral activity was directly proportional to the enzymatic activity of tyrosinases, since no antiviral capacity was observed for the inactive enzymes. The tyrosinases could represent a new antiviral inhibition mechanism through a catalytic mechanism of selective hydroxylation of key role tyrosine residues in viral proteases. The tyrosinases directly extracted from fresh mushroom (containing both tyrosinases) showed similar antiviral activity and, therefore, might provide low-cost drugs for the treatment of hepatitis C.

scholarly journals In Vitro Antiviral Activity of Tyrosinase from Mushroom Agaricus bisporus against Hepatitis C Virus

2021 ◽  
Vol 14 (8) ◽  
pp. 759
Author(s):  
David Lopez-Tejedor ◽  
Rafael Claveria-Gimeno ◽  
Adrian Velazquez-Campoy ◽  
Olga Abian ◽  
Jose M. Palomo
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Agaricus Bisporus ◽  
Catalytic Mechanism ◽  
Inhibition Mechanism ◽  
Viral Proteases ◽  
Inactive Form ◽  
Hepatitis C Virus Proteins

Tyrosinases from a commercial Agaricus bisporus protein extract and directly isolated from white mushrooms were purified in order to obtaining the well-known tyrosinase from A. bisporus (TyrAB) of 45 kDa and a newly discovered 50 kDa tyrosinase isoform (Tyr50 kDa), and tested showing high antiviral activity against the hepatitis C virus for the first time. Cell toxicity and antiviral activity of tyrosinases were determined in cultured Huh 5-2 liver tumor cells transfected with a replicon system (a plasmid that includes all non-structural hepatitis C virus proteins and replicates autonomously). TyrAB was able to inhibit the replication of the hepatitis C virus without inducing toxicity in liver cells. In addition, the post-translational isoform Tyr50 kDa showed higher antiviral capacity than the former (up to 10 times greater), also exhibiting 10 times higher activity than the commercial drug Ribavirin®. This antiviral activity was directly proportional to the enzymatic activity of tyrosinases, as no antiviral capacity was observed in the inactive form of the enzymes. The tyrosinases approach could represent a new antiviral inhibition mechanism, through a plausible catalytic mechanism of selective hydroxylation of the key role of tyrosine residues in viral proteases.

Suppression of Interferon-Induced Antiviral Activity in Cells Expressing Hepatitis C Virus Proteins

2000 ◽  
Vol 20 (12) ◽  
pp. 1111-1120 ◽  
Author(s):  
Hideki Aizaki ◽  
Sakura Saito ◽  
Toshio Ogino ◽  
Naoko Miyajima ◽  
Takashi Harada ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Hepatitis C Virus Proteins ◽  
In Cells ◽  
Virus Proteins

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.

Expression of hepatitis c virus proteins inhibits interferon α signaling in the liver of transgenic mice

2003 ◽  
Vol 124 (5) ◽  
pp. 1465-1475 ◽  
Author(s):  
Alex Blindenbacher ◽  
Francois H.T. Duong ◽  
Lukas Hunziker ◽  
Simone T.D. Stutvoet ◽  
Xueya Wang ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Transgenic Mice ◽  
Interferon Α ◽  
Hepatitis C Virus Proteins ◽  
Virus Proteins

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
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