Research on antiviral drugs and their mode of action in infected cells. in animals and in man. has led to a better understanding of the molecular pro cesses involved in virus replication. Screeninq of large numbers of natural and semisynthetic compounds resulted in the characterization of certain sub stances that had a limited efficiency as antiviral druqs. A few chemically synthesized compounds were also found to be effective as antiviral agents in the chemotherapy of human virus diseases. A major difficulty in the develop ment of effective antiviral agents has been the lack of selectivity. and toxicity for uninfected cells. of drugs that effectively inhibited virus replication in vitro. Further understanding of the molecular processes of virus replication in infected cells has resulted in the development of new antivirals directed at virus-coded enzymes or proteins. Recent studies on antivirals that are activated by the herpes simplex virus type l-coded thy midine kinase from a prod rug to an antiviral drug have opened new directions in the development of effective antiviral drugs. The present book deals with a number of antiviral drugs effective against herpes simplex viruses and provides some insight into the molecular aspects of virus replication. It also throws light on the new approaches to the development of antiviral drugs. The molecular basis of the antiviral activity of new and known drugs and their possible use in chemotherapy of viral disease are presented in this book.

One of the central problems in the study of the mechanism of DNA-ligand interactions is the existence and nature of sequence specificity with respect to the base pairs of DNA. The presence of such a specificity could be of particular significance because it might possibly mean the involvement of specific genes in the effectiveness of the different drugs. The elucidation of the factors responsible for the specificity could then be important for the development of compounds susceptible to contribute to the control of gene expression and also to the development of rationally conceived, improved new generations of effective and specific chemotherapeutic agents. Important recent achievements, experimental and theoretical, in the analysis of such sequence specificities open prospects for possible rapid progress in this field. The 23rd Jerusalem symposium was devoted to the exploration of these recent achievements in relation to many types of ligand, with special emphasis on antitumor drugs. All major types of interaction, intercalation, groove binding, covalent linking, coordination, have been considered. So was also the effect of the interaction on the structure and properties of the nucleic acids and the relationship between the interaction and biological or pharmacological activities. We feel that this Volume presents a relatively complete up-to-date account of the state of the art in this important field of research.

Since the discovery of HIV-l as the etiologic agent of acquired immunodeficiency syndrome (AIDS) in the early 1980s, remarkable progress has been made in both the basic understanding of the biological processes leading to AIDS and an accelerated effort in finding new treatments. As is often the case in rapidly advancing fields, most of the scientific discussions are best handled in specialized groups. The effort to organize a meeting on advances in molecular biology and targeted treatment for AIDS was an experiment of sorts to gather experts in selected areas of overlapping interests where advances in basic biology and its application in the development of new drugs could be discussed. Of necessity, the scope of the meeting had to be limited to maintain a certain focus. Important areas of rapid development in AIDS research, such as the vaccine development, epidemiology, animal models, etc. , had to be left out for more specialized meetings. The result, from all accounts, appeared to be quite a successful gathering, which provided a forum for informal discussions among scientists from industry and academic institutions. A remarkable feature of the AIDS virus is its genetic complexity and how some of its seemingly "extra genes" manage to regulate the normal functions of the host and most importantly its immune system.

Biological response modifiers are increasingly used in viral and cancer therapy. Since alterations of the immune system are the primary symptoms of HIV infection, especially therapies directed towards the modulation of the immune response have been under intense evaluation. This volume summarizes current knowledge of the interferon-based natural antiviral protection system including 2',5'-oligoadenylate and double-stranded RNA. It will also help to develop further a solid scientific rationale for the practical use of heterologous immunomodulators in the clinics.

Progress in molecular technology in recent years has caused an amazing growth of information about intercellular peptide messengers and their receptors. The number of characterized interleukins for example numbered just three six years ago and now there are at least 16. In addition, the number of described neutrophic peptides is around 30 and the number of receptors is ever increasing. Because many of these new peptide ligands and receptors were identified by "reverse genetic" techniques the understanding of their biological roles falls behind the knowledge of their molecular structures. However a new strain of functional studies has begun and animal models are developed allowing for further research into the biological roles of these messenger peptides and their receptors. Cytokines, the theme of this volume, describes a group of proteins identified primarily within the immune and hematopoietic systems. As many cytokines as possible are included along with their receptors providing the reader with a guide to an ever-changing field of scientific research.

The purpose of the series on Advances in Antiviral Drug Design is to regularly review the "state of the art" on emerging new developments in the antiviral drug research field, thereby spanning the conceptual design and chemical synthesis of new antiviral compounds, their structure-activity relationship, mechanism and target(s) of action, pharmacological behavior, antiviral activity spectrum, and therapeutic potential for clinical use. Volume 2 begins with a description of the antiviral potential of antisense oligonucleotides by J. Temsamani and S. Agrawal. According to the aims of the anitsense technology, these oligonucleotides should be targeted at specific viral antisense technology, these oligonucleotides should be targeted at specific viral mRNA sequences so that translation to the virus-specified proteins is blocked; this has been achieved for a number of oligomers, some of which are now in clinical trials for the treatment of HIV, HCMV, and human papilloma virus (HPV) infections. Then C.-S. Yuan, S. Liu, S.F. Wnuk, M.J. Robins and R.T. Borchardt assess the role of S-adenosylhornocysteine (AdoHcy) hydrolase as target for the design of antiviral agents with broad-spectrum antiviral activity. This is followed by an in-depth account on the design and synthesis of a number of first-, second- and third-generation AdoHcy hydrolase inhibitors and their mode of action at the enzyme level.V.E. Marquez provides a comprehensive description of the various carbocyclic (carba) nucleosides that have been synthesized and evaluated for antiviral activity. Although the number and diversity of the carba-nucleosides that have been found to be antivirally active (or inactive) is astonishingly high, there is no limit to further expansion of this fascinating class of molecules. For the various nucleoside analogues that have to be intracellularly phosphorylated to the 5'-triphosphate stage, to interact with their target enzyme (i.e., herpesviral DNA polymerase or retroviral revers transcriptase) the first phosphorylation step is often the rate-limiting step, and thus various strategies are envisaged by C. Perigoud, J.-L. Girardet, G. Gosselin and J.-L. Bach on how to bypass this initial phosphorylation and to deliver the nucleoside 5'-monophophate directly inside the cells.The HIV protease has been considered as a paradigm for rational drug design. The enzyme is among the best understood in terms of both structure and action, and because of its crucial role in the maturation of HIV, it has been vigorously pursued as a target for anti-HIV chemotherapy. In their comprehensive review of the multidisciplinary approach towards the development of HIV protease inhibitors A.G. Tomasselli, S. Thaisrivongs and R.L. Heinrikson highlight those protease inhibitors which have been brought forward to clinical trials.

Each issue lists papers published during the preceding year.

Provided here is a comprehensive examination of the basic and clinical condition of three innovative and promising approaches to cancer therapy, which may support or even substitute chemotherapy: differentiation, immunomodulation, and inhibition of angiogenesis. Differentiation shouldnormalize neoplastic cells and make them compatible with the host. Its feasibility with retinoids, interferons, chemotherapeutic and other agents is discussed. Modulation by biological agents, cytotoxic effector cells and drugs is considered in attempts to boost endogenous antitumour defenses and/or to render neoplastic cells more susceptible to the immune attack of the host. Finally, the important aspect of interfering with tumour blood vessel development and function is taken into account. Consideringthe importance that chemotherapy has in cancer treatment and in view of a more and more integrated strategy, the relationship between the aforementioned approaches and chemotherapeutic agents and chemoresistance is treated in detail.