C
Chao Lin
Researcher at Vertex Pharmaceuticals
Publications - 46
Citations - 4426
Chao Lin is an academic researcher from Vertex Pharmaceuticals. The author has contributed to research in topics: Hepatitis C virus & Protease. The author has an hindex of 23, co-authored 46 publications receiving 4385 citations.
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Journal ArticleDOI
Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide.
Joseph L. Kim,Morgenstern Kurt A,Chao Lin,Ted Fox,Maureen D. Dwyer,J. A. Landro,Stephen P. Chambers,William Markland,Christopher A. Lepre,Ethan O'malley,Scott L. Harbeson,Charles M. Rice,Murcko Mark A,Paul R. Caron,John A. Thomson +14 more
TL;DR: The 2.5 angstrom resolution X-ray crystal structure of the NS3 protease domain complexed with a synthetic NS4A activator peptide is reported, which shows a chymotrypsin-like fold and features a tetrahedrally coordinated metal ion distal to the active site.
Journal ArticleDOI
Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir.
Christoph Sarrazin,Tara L. Kieffer,Doug J. Bartels,Brian L. Hanzelka,Ute Müh,Martin W. Welker,Dennis Wincheringer,Yi Zhou,Hui–May Chu,Chao Lin,Christine J. Weegink,Henk W. Reesink,Stefan Zeuzem,Ann D. Kwong +13 more
TL;DR: Resistant HCV isolates are selected rapidly during therapy with the highly active protease inhibitor telaprevir, and changes in the frequency of mutations after the end of dosing showed an inverse relationship between in vivo viral fitness and resistance.
Journal ArticleDOI
Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding
Joseph L. Kim,Morgenstern Kurt A,James P. Griffith,Maureen D. Dwyer,John A. Thomson,Murcko Mark A,Chao Lin,Paul R. Caron +7 more
TL;DR: The structure of the HCV NS3 RNA helicase domain complexed with a single-stranded DNA oligonucleotide has been solved to 2.2 A resolution and is a member of a superfamily of helicases, termed superfamily II.
Journal ArticleDOI
Preclinical Profile of VX-950, a Potent, Selective, and Orally Bioavailable Inhibitor of Hepatitis C Virus NS3-4A Serine Protease
Robert B. Perni,Susan J. Almquist,Randal Byrn,Gurudatt Chandorkar,Pravin Chaturvedi,Lawrence F. Courtney,Caroline Decker,Kirk Dinehart,Cynthia A. Gates,Scott L. Harbeson,Angela D. Heiser,Gururaj Kalkeri,Elaine Kolaczkowski,Kai Lin,Yu-Ping Luong,B. Govinda Rao,William P. Taylor,John A. Thomson,Roger D. Tung,Yunyi Wei,Ann D. Kwong,Chao Lin +21 more
TL;DR: The overall preclinical profile of VX-950 supports its candidacy as a novel oral therapy against hepatitis C and a recently developed HCV protease mouse model showed excellent inhibition of HCV NS3-4A protease activity in the liver.
Journal ArticleDOI
In Vitro Resistance Studies of Hepatitis C Virus Serine Protease Inhibitors, VX-950 and BILN 2061 STRUCTURAL ANALYSIS INDICATES DIFFERENT RESISTANCE MECHANISMS
Chao Lin,Kai Lin,Yu-Ping Luong,B. Govinda Rao,Yunyi Wei,Debra L. Brennan,John R. Fulghum,Hsun-Mei Hsiao,Sue Ma,John Maxwell,Kevin M. Cottrell,Robert B. Perni,Cynthia A. Gates,Ann D. Kwong +13 more
TL;DR: In vitro resistance studies using a subgenomic replicon system to compare VX-950 with another HCV NS3·4A protease inhibitor, BILN 2061, are described and modeling analysis suggests that there are different mechanisms of resistance to V X-950 and BILn 2061.