Development of hepatitis C virus chimeric replicons for identifying broad spectrum NS3 protease inhibitors

2011 ◽  
Vol 91 (2) ◽  
pp. 102-111 ◽  
Author(s):  
Joseph Binder ◽  
Selwyna Tetangco ◽  
Megan Weinshank ◽  
Karen Maegley ◽  
Laura Lingardo ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Broad Spectrum ◽  
Ns3 Protease Inhibitors ◽  
Ns3 Protease

Development of Hepatitis C Virus (HCV) Chimeric Replicons for Identifying Broad Spectrum NS3 Protease Inhibitors

2007 ◽  
Vol 74 (3) ◽  
pp. A38-A38 ◽  
Author(s):  
J BINDER ◽  
S TETANGCO ◽  
M WICK ◽  
K MAEGLEY ◽  
L LINGARDO ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Broad Spectrum ◽  
Ns3 Protease Inhibitors ◽  
Ns3 Protease

Phenylglycine as a novel P2 scaffold in hepatitis C virus NS3 protease inhibitors

2007 ◽  
Vol 15 (3) ◽  
pp. 1448-1474 ◽  
Author(s):  
Pernilla Örtqvist ◽  
Shane D. Peterson ◽  
Eva Åkerblom ◽  
Thomas Gossas ◽  
Yogesh A. Sabnis ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Ns3 Protease Inhibitors ◽  
Ns3 Protease

scholarly journals Selection of Replicon Variants Resistant to ACH-806, a Novel Hepatitis C Virus Inhibitor with No Cross-Resistance to NS3 Protease and NS5B Polymerase Inhibitors

2008 ◽  
Vol 52 (6) ◽  
pp. 2043-2052 ◽  
Author(s):  
Wengang Yang ◽  
Yongsen Zhao ◽  
Joanne Fabrycki ◽  
Xiaohong Hou ◽  
Xingtie Nie ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Protease Inhibitors ◽  
Cross Resistance ◽  
Polymerase Inhibitors ◽  
Ns3 Protease Inhibitors ◽  
Ns3 Protease ◽  
Ns5b Polymerase ◽  
Selection Of

ABSTRACT We have discovered a novel class of compounds active against hepatitis C virus (HCV), using a surrogate cellular system, HCV replicon cells. The leading compound in the series, ACH-806 (GS-9132), is a potent and specific inhibitor of HCV. The selection of resistance replicon variants against ACH-806 was performed to map the mutations conferring resistance to ACH-806 and to determine cross-resistance profiles with other classes of HCV inhibitors. Several clones emerged after the addition of ACH-806 to HCV replicon cells at frequencies and durations similar to that observed with NS3 protease inhibitors and NS5B polymerase inhibitors. Phenotypic analyses of these clones revealed that they are resistant to ACH-806 but remain sensitive to other classes of HCV inhibitors. Moreover, no significant change in the susceptibility to ACH-806 was found when the replicon cellular clones resistant to NS3 protease inhibitors and NS5B polymerase inhibitors were examined. Sequencing of the entire coding region of ACH-806-resistant replicon variants yielded several consensus mutations. Reverse genetics identified two single mutations in NS3, a cysteine-to-serine mutation at amino acid 16 and an alanine-to-valine mutation at amino acid 39, that are responsible for the resistance of the replicon variants to ACH-806. Both mutations are located at the N terminus of NS3 where extensive interactions with the central hydrophobic region of NS4A exist. These data provide evidence that ACH-806 inhibits HCV replication by a novel mechanism.

Discovery of novel phosphonate derivatives as hepatitis C virus NS3 protease inhibitors

2009 ◽  
Vol 19 (13) ◽  
pp. 3453-3457 ◽  
Author(s):  
X. Christopher Sheng ◽  
Hyung-Jung Pyun ◽  
Kleem Chaudhary ◽  
Jianying Wang ◽  
Edward Doerffler ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Ns3 Protease Inhibitors ◽  
Ns3 Protease

scholarly journals Analysis of Naturally Occurring Resistant Mutations to Hepatitis C Virus NS3 Protease Inhibitors: A Preliminary Study in South of Iran

2015 ◽  
Vol 8 (10) ◽  
Author(s):  
Mozhgan Afrasiabi ◽  
Seyed Younes Hosseini ◽  
Ramin Yaghobi ◽  
Mohammad-Reza Fattahi ◽  
Maryam Ardebili ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Naturally Occurring ◽  
Ns3 Protease Inhibitors ◽  
Preliminary Study ◽  
Ns3 Protease

Pan-NS3 protease inhibitors of hepatitis C virus based on an R3-elongated pyrazinone scaffold

2018 ◽  
Vol 148 ◽  
pp. 453-464 ◽  
Author(s):  
Anna Karin Belfrage ◽  
Eldar Abdurakhmanov ◽  
Eva Åkerblom ◽  
Peter Brandt ◽  
Hiba Alogheli ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Ns3 Protease Inhibitors ◽  
Ns3 Protease
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