" . . . the motto for the therapeutics of the future will have to be de sedibus et causis pharmacorum. " P. EHRLICH, 1909 Exciting events in the basic disciplines of virology, immunology, and pharmacology continue to advance the understanding of the pathogenesis and control of virus diseases. At the same time, the rational development of antiviral agents is attracting, to an increasing extent, the interest of workers in other disciplines. Improvements in technology facilitate the definition of potential target sites for antiviral intervention and unmask new viral and host genes. The outcome is a further steady development of new antiviral agents which approach the "magic bullets" first proposed by PAUL EHRLICH. Remarkable advances in protein synthetic methods that yield polypeptides which inhibit active sites of viral proteins have aided substantially in the basic and clinical study of these antiviral agents. In addition, the extremely rapid progression in recombinant DNA techniques, leading to the synthesis of large quantities of gene products, is also increasing our opportunities at a dashing pace. New information and developing technology facilitate research on the mechanism of action, toxicity, pharmacokinetics, and pharmacodynamics of new agents. The list of clinically effective antiviral agents is expanding and the number of potentially useful compounds is growing rapidly. This book is a combined theoretical text and practical manual which, it is hoped, will be of use to all who have an interest in virus diseases, particularly scientists, physicians and graduate students.

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1 Pathogenesis of Viral Infections.- A. Introduction.- I. Defective Interfering Particles.- II. Integration of Viral Genomes.- B. Adenoviruses.- I. Structure and Replication.- II. Adenovirus Infections.- C. Arenaviruses.- D. Coronaviruses.- E. Viral Hepatitis.- I. Hepatitis A.- II. Hepatitis B.- F. Herpesviruses.- I. Herpes Simplex Viruses 1 and 2.- II. Herpes Simplex Virus Infections.- III. Cytomegalovirus.- IV. Varicella Zoster Virus.- V. Epstein-Barr Virus.- G. Orthomyxoviruses.- I. Influenza A and B Viruses.- II. Influenza C Virus.- III. Influenza Infections.- H. Human Papillomavirus.- J. Paramyxoviruses.- I. Measles Infection.- II. Persistent Measles Infection.- III. Mumps Infection.- IV. Parainfluenza Infection.- K. Picornaviruses.- I. Structure and Replication.- II. Picornavirus Infections.- L. Reoviruses.- M. RNA Tumor Viruses.- N. Rhabdoviruses.- I. Structure and Replication.- II. Rabies Virus Infection.- O. Rotaviruses.- I. Structure and Replication.- II. Rotavirus Infections.- P. Poxviruses.- I. Structure and Replication.- II. Poxvirus Infections.- Q. Togaviruses and Bunyaviruses.- I. Togaviruses.- II. Bunyaviruses.- R. Slow Viruses.- I. Unconventional Agents.- II. Conventional Agents.- References.- A.- 2 Pyrimidine Nucleosides with Selective Antiviral Activity.- A. Introduction.- B. 5-Halogenated Pyrimidine 2?-Deoxyribonucleosides.- I. 5-Iodo-2?-Deoxyuridine.- 1. Synthesis.- 2. Antiviral Activity.- 3. Effects on Normal Cells.- 4. Mechanism of Action.- II. 5-Trifluoromethyl-2?-Deoxyuridine.- 1. Synthesis.- 2. Antiviral Activity.- 3. Effects on Normal Cells.- 4. Mechanism of Action.- III. 5-Iodo-2?-Deoxycytidine.- 1. Synthesis.- 2. Antiviral Activity.- 3. Effects on Normal Cells.- 4. Mechanism of Action.- C. Other 5-Substituted 2?-Deoxyuridine Derivatives.- I. 5-Ethyl-2?-Deoxyuridine.- 1. Antiviral Activity.- 2. Effects on Normal Cells.- 3. Mechanism of Action.- II. 5-Propyl-2?-Deoxyuridine.- 1. Antiviral Activity.- 2. Mechanism of Action.- III. E-5-(2-Bromovinyl)-2?-Deoxyuridine (BVdUrd).- IV. 5-Methoxymethyl-2?-Deoxyuridine.- V. Miscellaneous 5-Substituted 2?-Deoxyuridine Derivatives.- D. Pyrimidine Nucleosides with an Altered Ring Structure.- E. Pyrimidine Nucleosides with an Altered Carbohydrate Moiety.- I. Arabinofuranosyltyymine.- 1. Antiviral Activity.- 2. Effects on Normal Cells.- 3. Mechanism of Action.- II. Arabinofuranosylcytosine.- III. 5-Iodo-5?-Amino-2?,5?-Dideoxyuridine.- 1. Synthesis.- 2. Antiviral Activity.- 3. Mechanism of Action.- IV. 1-(2-Deoxy-2-Fluoro-?-D-Arabinofuranosyl)-5-Iodocytosine.- References.- 3 Purines.- A. Introduction.- B. 9-?-D-Arabinofuranosyladenine.- I. Introduction and History.- II. Chemistry.- III. Antiviral Spectrum.- IV. Mechanism of Action.- V. Metabolism, Distribution, and Excretion.- VI. Clinical and Experimental Therapeutic Aspects.- VII. Untoward Effects.- VIII. Analogs of Ara-A.- IX. Perspectives.- C. 9-(2-Hydroxyethoxymethyl)guanine.- I. Introduction and History.- II. Chemistry.- III. Antiviral Spectrum.- IV. Mechanism of Action.- V. Metabolism, Distribution, and Excretion.- VI. Clinical and Experimental Therapeutic Aspects.- VII. Untoward Effects.- VIII. Perspectives.- References.- 4 Amantadine and Its Derivatives.- A. Introduction and History.- B. Chemical Structure.- C. Spectrum of Antiviral Activity.- D. Mechanism of Action.- E. Pharmacology.- I. Absorption.- II. Metabolism.- III. Side Effects.- F Animal Studies.- I. Prophylaxis.- II. Treatment.- G. Clinical Trials.- I. Prophylaxis.- II. Treatment.- H. Resistant Variants.- J. Conclusions and Perspectives.- References.- 5 The Thiosemicarbazones.- A. Introduction.- B. History.- C. Chemistry.- I. Aryl Thiosemicarbazones.- II. Quinoline, Pyridine, and Thiophene Thiosemicarbazones.- III. Isatin-?-Thiosemicarbazones.- 1. Substitution in the Aromatic Ring.- 2. N-Substitution in the Pyrrolidine Ring.- 3. Modification of the Pyrrolidine Ring.- 4. Modification of the TSC Side Chain.- 5. Other Compounds.- IV. Isatin-?-4?,4?-Dialkylthiosemicarbazones.- V. Isatin-?-Isothiosemicarbazones.- VI. Thiazole Thiosemicarbazones.- VII. Pyrrolidine and Pyrazolone Thiosemicarbazones.- VIII. Noncyclic Thiosemicarbazones.- IX. Miscellaneous Thiosemicarbazones.- D. Virus-Inhibitory Spectrum.- I. Aryl Thiosemicarbazones.- II. Quinoline, Pyridine, and Thiophene Thiosemicarbazones.- III. Isatin-?-Thiosemicarbazones.- IV. Isatin-?-4?,4?-Dialkylthiosemicarbazones.- V. Isatin-?-Isothiosemicarbazones.- VI. Thiazole Thiosemicarbazones.- VII. Pyrrolidine and Pyrazolone Thiosemicarbazones.- VIII. Noncyclic Thiosemicarbazones.- IX. Miscellaneous Thiosemicarbazones.- E. Effects on Normal Cells.- I. Aryl Thiosemicarbazones.- II. Quinoline, Pyridine, and Thiopene Thiosemicarbazones.- III. Isatin-?-Thiosemicarbazones.- IV. Isatin-?-4?, 4?-Dialkylthiosemicarbazones.- V. Isatin-?-Isothiosemicarbazones.- VI. Thiazole Thiosemicarbazones.- VII. Pyrrolidine and Pyrazolone Thiosemicarbazones.- VIII. Noncyclic Thiosemicarbazones.- IX. Miscellaneous Thiosemicarbazones.- F. Mechanism of Action.- I. Aryl Thiosemicarbazones.- II. Quinoline, Pyridine, and Thiopene Thiosemicarbazones.- III. Isatin-?-Thiosemicarbazones.- 1. Adsorption, Penetration, and Uncoating.- 2. Transcription.- 3. Translation.- 4. Replication.- 5. Proteins and Viral Assembly.- IV. Isatin-?-4?,4?-Dialkylthiosemicarbazones.- V. Isatin-?-Isothiosemicarbazones.- VI. Thiazole Thiosemicarbazones.- VII. Pyrrolidine and Pyrazolone Thiosemicarbazones.- VII. Noncyclic Thiosemicarbazones.- IX. Miscellaneous Thiosemicarbazones.- G. Animal Studies.- I. Aryl Thiosemicarbazones.- II. Quinoline, Pyridine, and Thiophene Thiosemicarbazones.- III. Isatin-?-Thiosemicarbazones.- IV. Isatin-?-4?,4?-Dialkylthiosemicarbazones.- V. Isatin-?-Isothiosemicarbazones.- VI. Thiazole Thiosemicarbazones.- H. Clinical Studies.- I. N1-Methylisatin-?-Thiosemicarbazone.- II. 3-Methyl-4-Bromo-5-Formylisothiazole Thiosemicarbazone.- J. Perspectives.- References.- 6 Interferon and Its Inducers.- A. Preface.- B. Introduction.- C. Production and Characterization of Human Interferons.- I. Classification.- II. Assay.- III. Production.- 1. Human Leukocyte Interferon.- 2. Human Fibroblast Interferon.- 3. Human Lymphoblastoid Interferon.- 4. Alternative Sources.- IV. Characterization.- 1. Protein Purification and Sequencing.- 2. Cloning of cDNA Corresponding to Interfero…