Research Briefings 1986 (1986) / Chapter Skim
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Report of the Research Briefing Panel on Prevention and Treatment of Viral Diseases
Report of the Research Briefing Panel on Prevention and Treatment of Viral Diseases
Pages 49-62
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Report of the Research Briefing Panel on Prevention and Treatment of Viral Diseases
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Staff Roy WidJus, Director, Division of International Health, Institute of Medicine Mark Feinberg, Consultant Alian R Hoffman, Executive Director, Committee on Science, Engineering, and Public Policy
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Infection profoundly affects the host cell, bestowing on it characteristics that distinguish it from uninfected cells. Viruses disrupt or kill infected cells or transform them into tumor ceils, thereby causing disease.
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Empirical approaches are not generally designed to yield drugs that are specific inhibitors of the functions of viral proteins and nucleic acids. Until very recently, most of the drugs examined have been general inhibitors of protein and nucleic acid synthesis, and a few happen to inhibit certain v~rusencoded enzymes somewhat more effectively than analogous host cell functions.
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technology, which permits the isolation and detailed molecular characterization of DNA or RNA, and the technology for producing monoclonal antibodies, which provides reagents not only for specific proteins but also for specific antigenic sites on specific proteins. Application of these methods has provided new insights into the structure of virus particles and surface proteins and into the regulation of virus multiplication.
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As a result, it is now known where the important epitopes on the influenza virus HA are, what the nature of the antibodies synthesized in response to individual epitopes is, and how single amino acid changes affect epitope function. Similar studies are in progress on several other viruses and viral surface components.
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In recent years, technical advances provided by recombinant DNA technology and the availability of monoclonal antibodies have led to a dramatic increase in knowlecige of the processes involved in virus multiplication and the interaction of viruses with their host cells. The following is an outline of current knowledge about virus multiplication and of the opportunities to inhibit it.
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are preferentially incorporated into viral nucleic acids and halt multiplication. Virus-encoded enzymes of nucleic acid synthesis-the RNA and DNA polymerases are, therefore, the most obvious targets for antiviral chemotherapy.
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Inhibition of Interactions of Viral and Host Cell Proteins with Regulatory Sequences in Viral Genomes Precise regulation is essential to the complex process of viral multiplication. Most, if not all, regulatory regions in viral genomes operate through interaction with proteins that have the ability to recognize and interact with specific nucleic acid sequences (i.e., they are sequence-specific binding proteins)
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The second target-cell approach takes advantage of the fact that virus-encoded proteins are incorporated into the membranes of infected host cells soon after infection. Monoclonal antibodies against such proteins can be produced and coupled to inhibitors of nucleic acid or protein synthesis that would normally not enter cells.
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in nucleic acid synthesis. Similar consideralions apply to disease caused by respiratory syncytial virus and the parainfluenzaviruses, which are also important human pathogens.
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The rotavirus multiplication cycle involves two different RNA-dependent RNA polymerases, which are therefore good targets for antiviral chemotherapy. Some rotavirus vaccine candiciates are in development, such as those based on bovine or rhesus rotaviruses; other candidates have been developer!
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1. The development of highly specific and potent antiviral drugs requires the colIaboration of scientists in several disciplines, among them protein chemists, enzyme kineticists, biophysicists, x-ray crystallographers, organic chemists, virolog~sts, cell biologists, pharmacologists, toxicologists, and clinicians.
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SUMMARY AND CONCLUSIONS Recent advances in molecular virology have laid the foundation for combating many viral diseases through new vaccines or more rational approaches to the development of antiviral drugs. These new approaches utilize recent advances in the knowledge of viral surfaces and of unique processes encoded by viral nucleic acid.
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