Nanhua Yao
Schering-Plough
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Featured researches published by Nanhua Yao.
Expert Opinion on Investigational Drugs | 2003
Michelle P. Walker; Nanhua Yao; Zhi Hong
Chronic hepatitis C virus (HCV) infection is the cause of an emerging global pandemic of chronic liver disease. Current pegylated IFN-α/ribavirin combination therapies are merely 54 – 56% efficacious and are often poorly tolerated. Popular strategies to improve upon existing therapies include efforts to decrease the dosing regime, improve the safety profile and specifically target the liver, the site of HCV replication. A clear goal of novel therapies is to significantly improve the therapeutic response for HCV-infected patients. One popular scheme to accomplish this is to directly target the viral enzymes involved in HCV RNA replication. While peptidomimetics have been pursued as potent and specific inhibitors of the serine protease, nucleoside analogues and non-nucleoside small molecules have been explored as RNA-dependent RNA polymerase inhibitors with promising potential. Advances in the understanding of HCV replication at the molecular level that stem from the use of the subgenomic replicon system, in vitro enzyme assays and from co-crystallographic structure solutions of the replication enzymes with novel inhibitors have propelled these compounds into clinical development. As these candidates are developed further, there is great hope for a cure for all those chronically infected with HCV.
Mini-reviews in Medicinal Chemistry | 2005
Jim Zhen Wu; Nanhua Yao; Michelle P. Walker; Zhi Hong
Lack of highly effective and safe therapeutics for hepatitis C virus (HCV) infection provides an opportunity as well as a challenge to discover novel and potent anti-HCV drugs. HCV NS5B RNA-dependent RNA polymerase (RdRp) is responsible for viral genome replication and thus constitutes a valid target for therapeutic intervention. To date, numerous HCV NS5B RdRp inhibitors have been discovered. This review focuses on the recent advances in discovery, mechanism of action studies and biological characterization of several distinct classes of potent inhibitors for NS5B RdRp. The clinical efficacy and developmental status of several promising compounds are also outlined.
Journal of Hepatology | 2000
Jacquelyn Wright-Minogue; Nanhua Yao; Rumin Zhang; Nancy Butkiewicz; Bahige M. Baroudy; Joseph Lau; Zhi Hong
BACKGROUND/AIMS Hepatitis C virus (HCV) nonstructural protein 3 (NS3) protease requires NS4A as a cofactor. This cofactor activity has been mapped to the central region of NS4A which interacts with the N-terminus of NS3 protease. To investigate whether this interaction is conserved among different genotypes of HCV cross-genotypic characterization were performed to delineate the importance of NS4A cofactor function in relation to the molecular evolution of HCV METHODS: Active NS3 protease domains of genotype 1-3 (representing five subtypes: la, 1b, 2a, 2b and 3a) were produced and purified from bacterial cells. NS4A cofactor-dependent in vitro trans cleavage assays were established using the in vitro translated recombinant protein substrates. These substrates contained the junction site of NS4A/NS4B, NS4B/NS5A or NS5A/NS5B. RESULTS Our data revealed that NS3 proteases cross-interacted with NS4A cofactors derived from different genotypes, although the genotype 2 cofactor was less efficient, which could be due to greater genetic variations in this region. Furthermore, the corresponding region in hepatitis G virus (HGV) NS4A was found to provide weak cofactor activity for HCV NS3 protease. Surprisingly, a synthetic substrate peptide from the NS4B/NS5A junction was also found to enhance HCV NS3 protease activity in a dose-dependent manner. CONCLUSION Our study suggests that the NS4A cofactor function is well conserved among HCV It is likely that other HCV-related viruses may have developed similar strategies to regulate their protease activity.
Virology | 2001
Zhi Hong; Craig E. Cameron; Michelle P. Walker; Christian Castro; Nanhua Yao; Johnson Y.N. Lau; Weidong Zhong
Bioorganic & Medicinal Chemistry Letters | 2007
I.W Cheney; Shunqi Yan; Todd Appleby; H Walker; T Vo; Nanhua Yao; Robert Hamatake; Zhi Hong; Jim Zhen Wu
Bioorganic & Medicinal Chemistry Letters | 2006
Martha de la Rosa; Hong Woo Kim; Esmir Gunic; Cheryl Jenket; Uyen Boyle; Yung-Hyo Koh; Ilia Korboukh; Matthew J. Allan; Weijian Zhang; Huanming Chen; Wen Xu; Shahul Nilar; Nanhua Yao; Robert Hamatake; Stanley Lang; Zhi Hong; Zhijun Zhang; Jean-Luc Girardet
Bioorganic & Medicinal Chemistry Letters | 2005
Ashok Arasappan; F.G. Njoroge; Tin-Yau Chan; Frank Bennett; Stephane L. Bogen; Kevin X. Chen; Haining Gu; Liwu Hong; Edwin Jao; Y.T. Liu; Raymond G. Lovey; Tejal N. Parekh; Russell E. Pike; Patrick A. Pinto; B. Santhanam; Srikanth Venkatraman; Henry A. Vaccaro; Hongwu Wang; Xiaozheng Yang; Zhaoning Zhu; Brian Mckittrick; Anil K. Saksena; Viyyoor M. Girijavallabhan; John Pichardo; Nancy Butkiewicz; Richard N. Ingram; B. Malcolm; Andrew Prongay; Nanhua Yao; B. Marten
Bioorganic & Medicinal Chemistry Letters | 2007
Shunqi Yan; Gary Larson; Jim Zhen Wu; Todd Appleby; Yili Ding; Robert Hamatake; Zhi Hong; Nanhua Yao
Bioorganic & Medicinal Chemistry Letters | 2006
Shunqi Yan; Todd Appleby; Gary Larson; Jim Zhen Wu; Robert Hamatake; Zhi Hong; Nanhua Yao
Bioorganic & Medicinal Chemistry Letters | 2007
Shunqi Yan; Todd Appleby; Gary Larson; Jim Zhen Wu; Robert Hamatake; Zhi Hong; Nanhua Yao