Use of X-Ray Crystallography in the Design of Antiviral Agents - 1st Edition - ISBN: 9780124387454, 9780323152457

Use of X-Ray Crystallography in the Design of Antiviral Agents

1st Edition

Editors: W Laver
eBook ISBN: 9780323152457
Imprint: Academic Press
Published Date: 28th February 1990
Page Count: 394
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Use of X-Ray Crystallography in the Design of Antiviral Agents describes materials presented at an International Workshop held in Kona, Hawaii on February 6-8, 1989, which discussed the use of X-ray crystallography in the design of antiviral agents.

This book focuses on the approach that determines the three-dimensional structures of viruses and virus proteins with biological activity, such as computer molecular modeling. The three-dimensional structures of a number of immune complexes that involve complexes of antigen with antibodies or peptide antigens complexed with an MHC molecule are also deliberated.

This text emphasizes that the three-dimensional structures allow the rational design of virus replication inhibitors that control virus infections in man and economically important domestic animals.

This publication is a good reference for pharmacists, biochemists, and clinicians researching on the design of antiviral agents.

Table of Contents




1. Membrane Fusion by Influenza Viruses and the Mechanism of Action of Amantadine

I. Studies on Membrane Fusion

II. The Mechanism of Action of Amantadine

III. Conclusions


2. Epitope Mapping and Idiotypy of the Antibody Response to Influenza Neuraminidase

I. Introduction

II. Identification of a Dominant Antigenic Site on N9 Neuraminidase

III. Anti-Idiotypes for Induction of Anti-N9 Neuraminidase Immune Responsiveness


3. Structure of a Human Histocompatibility Molecule: Implications for Its Interactions with Peptides and T Cell Receptors

I. Introduction

II. The Structure of HLA-A2

III. T Cell Receptor Structure

IV. Future Work and Implications for Drug Design


4. Structure of the Adenovirus Virion

I. Introduction

II. Virion Proteins

III. Hexon Structure

IV. Arrangement of Hexons in the Capsid

V. Position of Polypeptide IX

VI. Conclusions


5. Crystal Structures of Influenza Virus Neuraminidase Complexed with Monoclonal Antibody Fab Fragments

I. Introduction

II. The Influenza Virus Neuraminidase

III. Escape Mutants

IV. Structure of Escape Mutants

V. Structure of a Second N9 Neuraminidase-Fab Complex (NC 10 Fab)

VI. Mechanism of Inhibition of Neuraminidase Activity by Antibody

VII. Change in Antibody Structure

VIII. Influenza Type B Neuraminidase

IX. Sendai HN


6. An Approach to the Design of Anti-Influenza Agents

I. Introduction

II. Hemagglutinin Host-Cell Receptor Binding Site

III. Determination of Favorable Ligand Binding Regions in the Hemagglutinin Host-Cell Receptor Binding Site

IV. Design of Ligands to Block the Attachment of Influenza Viruses to Cells

V. Conclusions


7. Immunochemical and Crystallographic Studies on the Interaction between Antibody and a Synthetic Peptide of Influenza Hemagglutinin

I. Antigenic Properties of a Synthetic Peptide of Influenza Virus Hemagglutinin

II. Identification of the Amino Acid Residues Involved in Antibody Binding

III. Stoichiometry of the Interaction between Antibody and Peptide Antigen

IV. Properties of Anti-Idiotypic Antibodies Raised Against MAbs 1 /1 and 2/1

V. Conclusions


8. Structural Studies of Antipeptide Antibodies

I. Introduction

II. Anti-Hemagglutinin Peptide Fabs

III. Anti-Mhr Peptide Fabs


9. Complexes of Peptides, Nucleotides, and Fluorescein with Immunoglobulin Fragments: Effects of Solvent on Crystal Structures and Ligand Binding

I. Introduction

II. Binding Properties of the Meg Bence-Jones Dimer

III. Monoclonal Autoantibody with Activity against Single-Stranded DNA

IV. Three-Dimensional Structure of a Fluorescein-Fab Complex Crystallized in MPD


10. Neutralizing Rhino viruses with Antiviral Agents that Inhibit Attachment and Uncoating

I. Introduction

II. Canyon Structure

III. Alterations of the Canyon Shape that Inhibit Attachment

IV. Antiviral Agents that Interfere with Capsid Function

V. Conclusion


11. Structural Determinants of Serotype Specificity, Host Range, and Thermostability in Poliovirus

I. Introduction

II. Poliovirus Structure

III. Comparison of the Structures of P1/Mahoney and P3/Sabin

IV. Serotype-Specific Conformations in Antigenic Site 1

V. What Are the Determinants of Mouse Virulence?

VI. Molecular Modeling of Loop Structures in Poliovirus

VII. Newly Recognized Components of the Virion Structure

VIII. Temperature Sensitivity in the P3/Sabin Strain


12. Structure of Foot-and-Mouth Disease Virus

I. Introduction

II. Determination of the Three-Dimensional Structure

III. An Overview of the Structure of the Capsid

IV. Antigenic Surface of Foot-and-Mouth Disease Virus

V. Peptide Vaccines

VI. Cell Attachment Site

VII. Uncoating, Assembly, and Disassembly

VIII. Conclusions


13. Escape Mutant Analysis of a Drug-Binding Site can be Used to Map Functions in the Rhinovirus Capsid

I. Introduction

II. Results

III. Discussion


14. Quantitative Structure-Activity Relationships and Biological Consequences of Picornavirus Capsid-Binding Compounds

I. Introduction

II. Enantiomeric Effects

III. Structure-Activity Studies Based on Chain Length

IV. A Model for HRV14 Activity

V. Binding of Disoxaril

VI. Mechanism of Action

VII. Antiviral Activity in Virus-Infected Animals

VIII. Conclusions


15. Comparative Structures of Two Lysozyme-Antilysozyme Complexes

I. Introduction

II. HyHEL-5 and HyHEL-10 Fab Complexes with Lysozyme


16. Structural Basis of Antigen-Antibody Recognition

I. Introduction

II. Crystallographic Studies of Fab-Lysozyme Complexes

III. Idiotype-Anti-Idiotype Interactions

IV. Solubilization of the T Cell Antigen Receptor


17. Analysis of Antibody-Protein Interactions Utilizing Site-Directed Mutagenesis and a New Evolutionary Variant of Lysozyme

I. Introduction

II. Interactions of HyHEL-5 with HEL

III. Interactions of HyHEL-10 and HyHEL-8 with HEL

IV. Summation and Conclusion


18. Approaches toward the Design of Proteins of Enhanced Thermostability

I. Introduction

II. Hydrophobic Interactions

III. Hydrogen Bonding

IV. Helix-Dipole Interactions

V. Substitutions That Decrease the Entropy of Unfolding

VI. Removal of Strain

VII. Disulfide Bridges

VIII. Conclusions


19. Interplay among Enzyme Mechanism, Protein Structure, and the Design of Serine Protease Inhibitors

I. Introduction

II. Mechanism-Derived Inhibitors

III. Structure-Derived Inhibitors


20. Applications of Crystallographic Databases in Molecular Design

I. Introduction

II. Description of Crystallographic Databases

III. Molecular Design and Databases

IV. Examples of Database Utilization

V. Application to Design

VI. Conclusions


21. Virus Structure and the AIDS Problem: Strategies for Antiviral Design Based on Structure

I. Introduction

II. Overall Structure of HIV and Genomic Arrangement

III. A Detailed Look at the HIV Proteins in Light of Other Viral Structures

IV. Conclusion


22. Analysis of the Reverse Transcriptase of Human Immunodeficiency Virus Expressed in Escherichia Coli



23. Structural Studies on Human Immunodeficiency Virus Reverse Transcriptase

I. Introduction

II. Production and Purification of Recombinant HIV RT

III. Crystallization of HIV RT

IV. Results

V. Conclusions


24. Human Immunodeficiency Virus (Type 1) Protease: Enzymology and Three-Dimensional Structure of a New AIDS Drug Target

I. Introduction

II. Biochemistry of the HIV-1 Protease

III. Crystal Structure of the HIV-1 Protease


25. Oligomeric Structure of Retroviral Envelope Glycoproteins

I. Introduction

II. Materials and Methods

III. Results

IV. Discussion


26. Tumor Necrosis Factor: A Nonviral Jelly Roll

I. Introduction

II. Structure Determination

III. Structure

IV. Conclusions




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© Academic Press 1990
Academic Press
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W Laver

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