Journal ArticleDOI
Rational design of potent sialidase-based inhibitors of influenza virus replication.
Mark von Itzstein,Wen-Yang Wu,Gaik B. Kok,Michael S. Pegg,Jeffrey Clifford Dyason,Betty Jin,Tho Van Phan,Mark L. Smythe,Hume Forrest White,Hume Forrest White,Stuart W. Oliver,Peter M. Colman,Joseph N. Varghese,D. Michael Ryan,Jacqueline M. Woods,Richard C. Bethell,Vanessa J. Hotham,Janet M. Cameron,Charles R. Penn +18 more
TLDR
Two potent inhibitors based on the crystal structure of influenza virus sialidase have been designed and provide an example of the power of rational, computer-assisted drug design, indicating significant progress in the development of a new therapeutic or prophylactic treatment for influenza infection.Abstract:
Two potent inhibitors based on the crystal structure of influenza virus sialidase have been designed. These compounds are effective inhibitors not only of the enzyme, but also of the virus in cell culture and in animal models. The results provide an example of the power of rational, computer-assisted drug design, as well as indicating significant progress in the development of a new therapeutic or prophylactic treatment for influenza infection.read more
Citations
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Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function
Lin Chen,Simon N. Willis,Andrew H. Wei,Brian J. Smith,Jamie I. Fletcher,Mark G. Hinds,Peter M. Colman,Catherine L. Day,Jerry M. Adams,David C.S. Huang +9 more
TL;DR: The results suggest that apoptosis relies on selective interactions between particular subsets of these proteins and that it should be feasible to discover BH3-mimetic drugs that inactivate specific prosurvival targets.
Journal ArticleDOI
Biological Roles of Glycans
TL;DR: It is time for the diverse functional roles of glycans to be fully incorporated into the mainstream of biological sciences, as they are no different from other major macromolecular building blocks of life, simply more rapidly evolving and complex.
Journal ArticleDOI
How were new medicines discovered
David C. Swinney,Jason Anthony +1 more
TL;DR: It is postulate that a target-centric approach for first-in-class drugs, without consideration of an optimal MMOA, may contribute to the current high attrition rates and low productivity in pharmaceutical research and development.
Journal ArticleDOI
Molecular recognition of receptor sites using a genetic algorithm with a description of desolvation.
TL;DR: This work reports results based on software using a genetic algorithm that uses an evolutionary strategy in exploring the full conformational flexibility of the ligand with partial flexibility ofThe protein, and which satisfies the fundamental requirement that theligand must displace loosely bound water on binding.
Journal ArticleDOI
Virtual screening of chemical libraries.
TL;DR: Interest in virtual screening is re-ignited, which is now widely used in drug discovery, albeit on a more limited scale than empirical screening.
References
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A computational procedure for determining energetically favorable binding sites on biologically important macromolecules.
TL;DR: The interaction of a probe group with a protein of known structure is computed at sample positions throughout and around the macromolecule, giving an array of energy values.
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Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution.
TL;DR: The haemagglutinin glycoprotein of influenza virus is a trimer comprising two structurally distinct regions: a triple-stranded coiled-coil of α-helices extends 76 Å from the membrane and a globular region of antiparallel β-sheet is positioned on top of this stem.
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Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation
TL;DR: Four ‘antigenic sites’ on the three-dimensional structure of the influenza haemagglutinin are identified and at least one amino acid substitution in each site seems to be required for the production of new epidemic strains between 1968 and 1975.
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Influenza virus M2 protein has ion channel activity.
TL;DR: Analysis of the currents of altered M2 proteins suggests that the channel pore is formed by the transmembrane domain of the M2 protein, which is proposed to have a pivotal role in the biology of influenza virus infection.
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Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 Å resolution
TL;DR: The tetrameric enzyme has circular 4-fold symmetry stabilized in part by metal ions bound on the symmetry axis, and sugar residues are attached to four of the five potential glycosylation sequences, and in one case contribute to the interaction between subunits in the tetramer.