Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
chemical engineering
Detailed computational study of the active site of the hepatitis C viral rna polymerase to aid novel drug design
Journal of Chemical Information and Modeling, Volume 53, No. 11, Year 2013
Notification
URL copied to clipboard!
Description
The hepatitis C virus (HCV) RNA polymerase, NS5B, is a leading target for novel and selective HCV drug design. The enzyme has been the subject of intensive drug discovery aimed at developing direct acting antiviral (DAA) agents that inhibit its activity and hence prevent the virus from replicating its genome. In this study, we focus on one class of NS5B inhibitors, namely nucleos(t)ide mimetics. Forty-one distinct nucleotide structures have been modeled within the active site of NS5B for the six major HCV genotypes. Our comprehensive modeling protocol employed 287 different molecular dynamics simulations combined with the molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) methodology to rank and analyze these structures for all genotypes. The binding interactions of the individual compounds have been investigated and reduced to the atomic level. The present study significantly refines our understanding of the mode of action of NS5B-nucleotide-inhibitors, identifies the key structural elements necessary for their activity, and implements the tools for ranking the potential of additional much needed novel inhibitors of NS5B. © 2013 American Chemical Society.
Authors & Co-Authors
Barakat, Khaled H.
Canada, Edmonton
Li ka Shing Institute of Virology
Egypt, Fayoum
Fayoum University
Law, John
Canada, Edmonton
Li ka Shing Institute of Virology
Prunotto, Alessio
Italy, Turin
Politecnico Di Torino
Magee, Wendy C.
Canada, Edmonton
Li ka Shing Institute of Virology
Evans, David H.
Canada, Edmonton
Li ka Shing Institute of Virology
Tyrrell, David Lorne John
Canada, Edmonton
Li ka Shing Institute of Virology
Tuszynski, J. A.
Canada, Edmonton
University of Alberta
Houghton, Michael A.
Canada, Edmonton
Li ka Shing Institute of Virology
Statistics
Citations: 30
Authors: 8
Affiliations: 4
Identifiers
Doi:
10.1021/ci4003969
ISSN:
15499596
e-ISSN:
1549960X
Research Areas
Infectious Diseases