Results 191 to 200 of about 17,579 (227)

Enantioselective Synthesis of an HCV NS5a Antagonist

Organic Letters, 2014
A concise, enantioselective synthesis of the HCV NS5a inhibitor MK-8742 (1) is reported. The features of the synthesis include a highly enantioselective transfer hydrogenation of an NH imine and a dynamic diastereoselective transformation. The synthesis of this complex target requires simple starting materials and nine linear steps for completion.
Ian K, Mangion, Cheng-yi, Chen, Hongmei, Li, Peter, Maligres, Yonggang, Chen, Melodie, Christensen, Ryan, Cohen, Ingyu, Jeon, Artis, Klapars, Shane, Krska, Hoa, Nguyen, Robert A, Reamer, Benjamin D, Sherry, Ilia, Zavialov   +13 more
openaire   +2 more sources

The NS5A Replication Complex Inhibitors: Difference Makers?

Clinics in Liver Disease, 2011
The development and approval of direct-acting antiviral agents looks set to transform the treatment of chronic hepatitis C infection. Among the agents in development are novel compounds that inhibit the function of the NS5A protein: a pleiotropic protein with a complex and essential role in viral replication.
Robert G, Gish, Nicholas A, Meanwell
openaire   +2 more sources

The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein

Virology, 2011
The hepatitis C virus (HCV) non-structural (NS) 5A protein plays an essential role in the replication of the viral RNA by the membrane-associated replication complex (RC). Recently, a putative NS5A inhibitor, BMS-790052, exhibited the highest potency of any known anti-HCV compound in inhibiting HCV replication in vitro and showed a promising clinical ...
Choongho Lee, Ella H Sklan, Jeffrey S Glenn   +2 more
exaly   +3 more sources

Prevalence of NS5A resistance associated variants in NS5A inhibitor treatment failures and an effective treatment for NS5A-P32 deleted hepatitis C virus in humanized mice

Biochemical and Biophysical Research Communications, 2018
Patients with chronic hepatitis C virus (HCV) infection who have failed to respond to direct-acting antiviral (DAA) treatment often acquire drug resistance-associated variants (RAVs). The NS5A-P32 deletion (P32del) RAV confers potent resistance to NS5A inhibitors; therefore, patients who acquire this deletion are likely to fail to respond to DAA re ...
Yuji Teraoka, Takuro Uchida, Michio Imamura, Mitsutaka Osawa, Masataka Tsuge, Hiromi Abe-Chayama, C. Nelson Hayes, Grace Naswa Makokha, Hiroshi Aikata, Daiki Miki, Hidenori Ochi, Yuji Ishida, Chise Tateno, Kazuaki Chayama   +13 more
openaire   +2 more sources

Prevalence of Natural Polymorphisms at the HCV Ns5A Gene Associated with Resistance to Daclatasvir, An Ns5A Inhibitor

Antiviral Therapy, 2012
Background Daclatasvir (BMS-790052) is an investigational molecule that inhibits the HCV NS5A protein and shows potent antiviral activity apparently across all HCV genotypes. Selection of drug resistance mutations has been reported only for HCV genotype 1, and no information exists for other HCV variants and/or in HIV–HCV-coinfected individuals ...
Plaza, Zulema, Soriano, Vincent, Vispo, Eugenia, del Mar Gonzalez, Maria, Barreiro, Pablo, Seclén, Eduardo, Poveda, Eva   +6 more
openaire   +2 more sources

HCV NS5A Inhibitors in Development

Clinics in Liver Disease, 2013
NS5A protein plays a key role in hepatitis C virus (HCV) replication. Daclatasvir (DCV, BMS-790052) is a first-in-class inhibitor of the HCV NS5A replication complex with potent antiviral activity but a low barrier to resistance. DCV as triple therapy in combination with pegylated interferon and ribavirin resulted in a high rate of early virologic ...
openaire   +2 more sources

Discovery of potent macrocyclic HCV NS5A inhibitors

Bioorganic & Medicinal Chemistry Letters, 2016
HCV NS5A inhibitors have demonstrated impressive in vitro virologic profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed-dose combination (FDC) regimen for the treatment of HCV infection.
Wensheng Yu, Bancha Vibulbhan, Stuart B. Rosenblum, Gregory S. Martin, A. Samuel Vellekoop, Christian L. Holst, Craig A. Coburn, Michael Wong, Oleg Selyutin, Tao Ji, Bin Zhong, Bin Hu, Lei Chen, Michael P. Dwyer, Yueheng Jiang, Anilkumar G. Nair, Ling Tong, Qingbei Zeng, Sony Agrawal, Donna Carr, Laura Rokosz, Rong Liu, Stephanie Curry, Patricia McMonagle, Paul Ingravallo, Fred Lahser, Ernest Asante-Appiah, James Fells, Joseph A. Kozlowski   +28 more
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Ser235 phosphorylation of hepatitis C virus NS5A is required for NS5A dimerization and drug resistance

Life Sciences
Hepatitis C virus (HCV) infection is recognized as a major causative agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV non-structural protein 5A (NS5A) is a dimeric phosphoprotein with a hyperphosphorylated form to act as a switch that regulates HCV replication and assembly.
Wei-Ping, Lee, Keng-Chang, Tsai, Shi-Xian, Liao, Yi-Hsiang, Huang, Ming-Chih, Hou, Keng-Hsin, Lan   +5 more
openaire   +2 more sources

Ser38‐His93‐Asn91 triad confers resistance of JFH1 HCV NS5A‐Y93H variant to NS5A inhibitors

The FEBS Journal
HCV NS5A is a dimeric phosphoprotein involved in HCV replication. NS5A inhibitors are among direct‐acting antivirals (DAA) for HCV therapy. The Y93H mutant of NS5A is resistant to NS5A inhibitors, but the precise mechanism remains unclear. In this report, we proposed a Ser38‐His93‐Asn91 triad to dissect the mechanism. Using
Wei‐Ping Lee, Keng‐Chang Tsai, Shi‐Xian Liao, Yi‐Hsiang Huang, Ming‐Chih Hou, Keng‐Hsin Lan   +5 more
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NS5A Phosphorylation and Hyperphosphorylation

2009
NS5A phosphorylation can be studied in two ways: in living cells and in vitro. The former has several advantages: NS5A phosphorylation takes place in a cellular background and therefore might mimic more closely the real in vivo situation. Viral proteins and cellular kinases are in the correct cellular compartments, and dynamic processes like viral ...
openaire   +2 more sources