Results 21 to 30 of about 3,421,850 (195)

The Discovery of Potent Nonstructural Protein 5A (NS5A) Inhibitors with a Unique Resistance Profile—Part 1

ChemMedChem, 2014
Nonstructural protein 5A (NS5A) represents a novel target for the treatment of hepatitis C virus (HCV). Daclatasvir, recently reported by Bristol–Myers–Squibb, is a potent NS5A inhibitor currently under investigation in phase 3 clinical trials. While the
Dayal, Satish, Milbank, Jared, Nichols, Carly, Florian Wakenhut, David C. Blakemore, Rebecca Glen, Duncan Hay, Michael Paradowski, Rebecca Halstead, Jared Milbank, Wakenhut, Florian, Smith-Burchnell, Caroline, David C. Pryde, Chris Pickford, Fiona Adam, Pryde, David C., Blakemore, David C., Wilson, Craig P., Pike, Andrew, Caroline Smith‐Burchnell, Shaw, Stephen, Stephen Shaw, Adam, Fiona, Andrew Pike, Lesa Watson, Paradowski, Michael, Rebecca A. Brimage, Jean‐Yves Chiva, Tran, Thien Duc, Hay, Duncan, Thien Duc Tran, Rob Webster, Halstead, Rebecca, Chiva, Jean-Yves, Westby, Mike, Mike Westby, Gardner, Iain, Pickford, Chris, Glen, Rebecca, Satish Dayal, Carly Nichols, Brimage, Rebecca A., Webster, Rob, Watson, Lesa, Iain Gardner, Craig P. Wilson   +45 more
core   +3 more sources

The hepatitis C viral nonstructural protein 5A stabilizes growth-regulatory human transcripts. [PDF]

Nucleic Acids Res, 2020
AbstractNumerous mammalian proto-oncogene and other growth-regulatory transcripts are upregulated in malignancy due to abnormal mRNA stabilization. In hepatoma cells expressing a hepatitis C virus (HCV) subgenomic replicon, we found that the viral nonstructural protein 5A (NS5A), a protein known to bind to viral RNA, also bound specifically to human ...
Guo L, Sharma SD, Debes JD, Beisang D, Rattenbacher B, Louis IV, Wiesner DL, Cameron CE, Bohjanen PR.   +8 more
europepmc   +6 more sources

The Discovery of Potent Nonstructural Protein 5A (NS5A) Inhibitors with a Unique Resistance Profile—Part 2

ChemMedChem, 2014
In ongoing studies towards novel hepatitis C virus (HCV) therapeutics, inhibitors of nonstructural protein 5A (NS5A) were evaluated. Specifically, starting from previously reported lead compounds, peripheral substitution patterns of a series of biaryl ...
Dayal, Satish, Nichols, Carly, David C. Blakemore, Duncan Hay, Wakenhut, Florian, David C. Pryde, Chris Pickford, Fiona Adam, Pryde, David C., David Leese, Cheung, Kathy, Pike, Andrew, Caroline Smith‐Burchnell, Shaw, Stephen, Stephen Shaw, Felice Daverio, Andrew Pike, Statham, Keith, Lesa Watson, Jean‐Yves Chiva, Darren Stead, Roberts, Lee R., Rob Webster, Chiva, Jean-Yves, Lee R. Roberts, Satish Dayal, Carly Nichols, David Stonehouse, Webster, Rob, Watson, Lesa, Samuel Crook, Milbank, Jared, Florian Wakenhut, Michael Paradowski, Keith Statham, Jared Milbank, Smith-Burchnell, Caroline, Blakemore, David C., Wybrow, Robert, Adam, Fiona, Paradowski, Michael, Daverio, Felice, Tran, Thien Duc, Hay, Duncan, Gilles H. Goetz, Thien Duc Tran, Robert Wybrow, Kathy Cheung, Crook, Samuel, Stonehouse, David, Westby, Mike, Mike Westby, Gardner, Iain, Pickford, Chris, Ye Che, Stead, Darren, Goetz, Gilles H., Leese, David, Che, Ye, Iain Gardner   +59 more
core   +3 more sources

Sequential S232/S235/S238 Phosphorylation of the Hepatitis C Virus Nonstructural Protein 5A. [PDF]

J Virol, 2018
The nonstructural protein 5A (NS5A) of the hepatitis C virus was thought to undergo sequential intramolecular phosphorylation on a series of serine residues; however, direct evidence was missing. We offer the first direct evidence of a CKIα-mediated intramolecular sequential NS5A phosphorylation cascade from serine 232 through 235 to 238.
Hsu SC, Tsai CN, Lee KY, Pan TC, Lo CW, Yu MJ.   +5 more
europepmc   +4 more sources

Resistance analysis of genotype 3 hepatitis C virus indicates subtypes inherently resistant to nonstructural protein 5A inhibitors. [PDF]

Hepatology, 2019
Hepatitis C virus (HCV) genotype (gt) 3 is highly prevalent globally, with non-gt3a subtypes common in Southeast Asia. Resistance-associated substitutions (RASs) have been shown to play a role in treatment failure. However, the role of RASs in gt3 is not
Smith D, Magri A, Bonsall D, Ip CLC, Trebes A, Brown A, Piazza P, Bowden R, Nguyen D, Ansari MA, Simmonds P, Barnes E, STOP-HCV Consortium.   +12 more
europepmc   +2 more sources

Regulation of neuronal proapoptotic potassium currents by the hepatitis C virus nonstructural protein 5A. [PDF]

J Neurosci, 2012
Apoptosis-enabling neuronal potassium efflux is mediated by an enhancement of K+ currents. In cortical neurons, increased currents are triggered by dual phosphorylation of Kv2.1 by Src and p38 at channel residues Y124 and S800. It was recently shown that a K+ current surge is also present in hepatocytes undergoing apoptosis, and that the hepatitis C ...
Norris CA, He K, Springer MG, Hartnett KA, Horn JP, Aizenman E.   +5 more
europepmc   +4 more sources

Identification of novel neutralizing determinants for protection against HCV

Hepatology, EarlyView., 2022
Identification of novel neutralizing determinants for protection against hepatitis C virus. Abstract Background and Aims HCV evasion of neutralizing antibodies (nAb) results in viral persistence and poses challenges to the development of an urgently needed vaccine.
Garazi P. Alzua, Anne F. Pihl, Anna Offersgaard, Rodrigo Velázquez‐Moctezuma, Carlos R. Duarte Hernandez, Elias H. Augestad, Ulrik Fahnøe, Christian K. Mathiesen, Henrik Krarup, Mansun Law, Jannick Prentoe, Jens Bukh, Judith M. Gottwein   +12 more
wiley   +1 more source

Inhibition of cellular protein secretion by norwalk virus nonstructural protein p22 requires a mimic of an endoplasmic reticulum export signal. [PDF]

, 2013
Protein trafficking between the endoplasmic reticulum (ER) and Golgi apparatus is central to cellular homeostasis. ER export signals are utilized by a subset of proteins to rapidly exit the ER by direct uptake into COPII vesicles for transport to the ...
Estes, M. K., Guix Arnau, Susana, Katayama, K., Crawford, Sue E., Sharp, T. M.   +4 more
core   +3 more sources

Characterization of a Threonine-Rich Cluster in Hepatitis C Virus Nonstructural Protein 5A and Its Contribution to Hyperphosphorylation. [PDF]

J Virol, 2018
Hepatitis C virus infections affect 71 million people worldwide and cause severe chronic liver disease. Recently, efficient antiviral therapies have been established, with inhibitors of nonstructural protein NS5A as a cornerstone. NS5A is a central regulator of HCV replication and assembly but is still enigmatic in its molecular functions. It exists in
Schenk C, Meyrath M, Warnken U, Schnölzer M, Mier W, Harak C, Lohmann V.   +6 more
europepmc   +4 more sources

Role of nonstructural protein NS2A in flavivirus assembly [PDF]

, 2008
Flavivirus nonstructural (NS) proteins are involved in RNA replication and modulation of the host antiviral response; however, evidence is mounting that some NS proteins also have essential roles in virus assembly.
Pijlman, G.P., Leung, J.Y., Khromykh, A.A., Hyde, J., Kondratieva, N., Mackenzie, J.M.   +5 more
core   +1 more source