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

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

1st Edition - January 1, 1990

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  • Editor: W Laver
  • eBook ISBN: 9780323152457

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Description

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


  • Contributors

    Foreword

    Preface

    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

    References

    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

    References

    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

    References

    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

    References

    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

    References

    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

    References

    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

    References

    8. Structural Studies of Antipeptide Antibodies

    I. Introduction

    II. Anti-Hemagglutinin Peptide Fabs

    III. Anti-Mhr Peptide Fabs

    References

    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

    References

    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

    References

    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

    References

    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

    References

    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

    References

    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

    References

    15. Comparative Structures of Two Lysozyme-Antilysozyme Complexes

    I. Introduction

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

    References

    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

    References

    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

    References

    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

    References

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

    I. Introduction

    II. Mechanism-Derived Inhibitors

    III. Structure-Derived Inhibitors

    References

    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

    References

    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

    References

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

    Text

    References

    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

    References

    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

    References

    25. Oligomeric Structure of Retroviral Envelope Glycoproteins

    I. Introduction

    II. Materials and Methods

    III. Results

    IV. Discussion

    References

    26. Tumor Necrosis Factor: A Nonviral Jelly Roll

    I. Introduction

    II. Structure Determination

    III. Structure

    IV. Conclusions

    References

    Index

Product details

  • No. of pages: 394
  • Language: English
  • Copyright: © Academic Press 1990
  • Published: January 1, 1990
  • Imprint: Academic Press
  • eBook ISBN: 9780323152457

About the Editor

W Laver

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