hepatitis/protease

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Protease inhibitor therapy for hepatitis C virus-infection.

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Prijava / prijava

BACKGROUND The hepatitis C virus (HCV) has affected an estimated of 80 million individuals worldwide and is a strain on public health. Around 25-30% of patients in Europe and the US who are infected with HIV are coinfected with HCV. Prior to 2013, treatment modalities containing an NS3/4A protease

Synergy of a hepatitis C virus (HCV) NS4A antagonist in combination with HCV protease and polymerase inhibitors.

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Prijava / prijava

Rapid emergence of resistance to monotherapy with virus-specific inhibitors necessitates combination therapy. ACH-806 is a hepatitis C virus NS4A inhibitor with a novel mechanism of action and resistance pathway. This compound was synergistic with NS3 protease inhibitors and NS5B nucleoside and

Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir (BMS-650032).

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Prijava / prijava

Asunaprevir (ASV; BMS-650032) is a hepatitis C virus (HCV) NS3 protease inhibitor that has demonstrated efficacy in patients chronically infected with HCV genotype 1 when combined with alfa interferon and/or the NS5A replication complex inhibitor daclatasvir. ASV competitively binds to the NS3/4A

Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir.

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OBJECTIVE Telaprevir (VX-950), a hepatitis C virus (HCV) NS3.4A protease inhibitor, has shown strong antiviral activity in phase 1 clinical studies. Because of high levels of HCV replication and the low fidelity of HCV polymerase, selection of resistant isolates during therapy may occur. METHODS A

In vitro resistance studies of hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061: structural analysis indicates different resistance mechanisms.

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Prijava / prijava

We have used a structure-based drug design approach to identify small molecule inhibitors of the hepatitis C virus (HCV) NS3.4A protease as potential candidates for new anti-HCV therapies. VX-950 is a potent NS3.4A protease inhibitor that was recently selected as a clinical development candidate for

1-Aminocyclopropaneboronic acid: synthesis and incorporation into an inhibitor of hepatitis C virus NS3 protease.

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Prijava / prijava

The previously unreported alpha,alpha-disubstituted 1-aminoboronate esters have potential utility in peptidomimetic design, particularly against serine protease targets. A concise synthesis of 1-aminocyclopropaneboronate pinanediol ester is reported, and a peptidyl derivative is shown to have modest

Telaprevir: an oral protease inhibitor for hepatitis C virus infection.

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OBJECTIVE The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, drug interactions, viral drug resistance, dosage and administration, and place in therapy of telaprevir are reviewed. CONCLUSIONS Telaprevir is an oral NS3/4A protease inhibitor that was recently approved by

Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection.

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Prijava / prijava

More than 170 million people worldwide are affected by the hepatitis C virus (HCV). The disease has been described as a "silent epidemic" and "a serious global health crisis". HCV infection is a leading cause of chronic liver disease such as cirrhosis, carcinoma, or liver failure. The current

Mutations conferring resistance to a hepatitis C virus (HCV) RNA-dependent RNA polymerase inhibitor alone or in combination with an HCV serine protease inhibitor in vitro.

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Prijava / prijava

Compounds A-782759 (an N-1-aza-4-hydroxyquinolone benzothiadiazine) and BILN-2061 are specific anti-hepatitis C virus (HCV) agents that inhibit the RNA-dependent RNA polymerase and the NS3 serine protease, respectively. Both compounds display potent activity against HCV replicons in tissue culture.

Protease 3C of hepatitis A virus induces vacuolization of lysosomal/endosomal organelles and caspase-independent cell death.

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Prijava / prijava

BACKGROUND 3C proteases, the main proteases of picornaviruses, play the key role in viral life cycle by processing polyproteins. In addition, 3C proteases digest certain host cell proteins to suppress antiviral defense, transcription, and translation. The activity of 3C proteases per se induces host

Allosteric inhibitors of the NS3 protease from the hepatitis C virus.

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Prijava / prijava

The nonstructural protein 3 (NS3) from the hepatitis C virus processes the non-structural region of the viral precursor polyprotein in infected hepatic cells. The NS3 protease activity has been considered a target for drug development since its identification two decades ago. Although specific

Safety and efficacy of protease inhibitors to treat hepatitis C after liver transplantation: a multicenter experience.

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Prijava / prijava

OBJECTIVE Protease inhibitors (PI) with peginterferon/ribavirin have significantly improved SVR rates in HCV G1 patients. Their use to treat HCV recurrence after liver transplantation (LT) is a challenge. METHODS This cohort study included 37 liver transplant recipients (male, 92%, age 57 ± 11

The protease inhibitor, GS-9256, and non-nucleoside polymerase inhibitor tegobuvir alone, with ribavirin, or pegylated interferon plus ribavirin in hepatitis C.

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Prijava / prijava

Tegobuvir (GS-9190), a non-nucleoside nonstructural protein (NS)5B polymerase inhibitor, and GS-9256, an NS3 serine protease inhibitor, individually have activity against hepatitis C virus (HCV) genotype 1. The antiviral activity of tegobuvir and GS-9256 as oral combination therapy, or together with

A complete mutational fitness map of the hepatitis C virus nonstructural 3 protease: relation to recognition by cytotoxic T lymphocytes.

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Prijava / prijava

The hepatitis C virus nonstructural (NS) 3/4A protease sequence is highly conserved for reasons not fully understood. We determined the protease activity in 181 NS3/4A gene products in which each protease residue was replaced by alanine or glycine. Unexpectedly, most (87%) protease residues could be

Discovery of achiral inhibitors of the hepatitis C virus NS3 protease based on 2(1H)-pyrazinones.

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Prijava / prijava

Herein, the design, synthesis and inhibitory potency of a series of novel hepatitis C virus (HCV) NS3 protease inhibitors are presented. These inhibitors are based on a 2(1H)-pyrazinone P3 scaffold in combination with either a P2 phenylglycine or a glycine, and they were evaluated on the wild type

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