How to keep your favourite virus in check

Abstract

Antiviral Agents: Advances and Problemsedited by E. Jucker, Birkhauser, 2001. DM130 (paperback) (viii + 258 pages) ISBN 3 7643 6547 1Viral infections of all kinds have a significant impact on public health, and nowadays it looks as if this impact is ever increasing. Although many of the pathogenic viruses are old companions of mankind, the pandemias of both the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) emerged only in the 20th century. In the struggle with pathogens we distinguish between the treatment of disease and protection against the disease. Protection against infectious disease was pioneered by the work of Jenner with vaccinia virus two centuries ago, and resulted in what is today known as vaccination. Jenner's approach culminated, 170 years later, in victory over small pox, the first and only example of a pathogen's eradication. Ironically, while vaccination against viral diseases resulted in further successes (particularly against, for example, polio and yellow fever) and while the advent of antibiotics equipped mankind to fight bacterial infections, there was virtually no progress in the therapy, let alone cure, of viral diseases. However, early attempts with rather unspecific compounds such as idoxuridine or amantadine permitted the identification of specific requirements and pitfalls of antiviral therapies. Because viral replication is intimately linked to host cell metabolism, it proved difficult to achieve acceptable therapeutic indices (efficacy versus toxicity). Thus, it was (and still is) essential to identify and characterize virally encoded proteins, preferentially enzymes, as potential drug targets that were specific for the viral life cycle. This requirement is also illustrated by the fact that nearly all early antiviral agents are nucleotide analogues, aimed at the suppression of the virus’ polymerase. It was however only in the 1980s, with the advent of acyclovir, that a compound that selectively inhibited viral enzymes was found. Since then, the list of approved antiviral agents has grown, but most of these result from the tremendous efforts to cope with the HIV epidemic, with the known considerable, but still limited, success. Unfortunately, because many viruses have a propensity to develop latency, the difference between treatment and cure becomes only too clear.The aim of Antiviral Agents: Advances and Problems is to introduce practitioners and advanced students to different viruses, to confront them with the latest research developments in addition to shortcomings of current treatment, and to indicate future directions. This book is the first volume of a ‘special topic’ series (which is to appear once a year, the following issue dealing with fungi) and contains updated review articles that were published earlier in Progress in Drug Research. There are six contributions, covering HIV, influenza, HCV, hepatitis B virus (HBV), herpesviruses and picornaviruses. An instructive and near-to-comprehensive overview of current knowledge is provided for each virus covered, listing the different antiviral drugs available including those in clinical and preclinical testing. The inclusion of overviews on molecular biology in addition to in vitro and animal models used to study HCV and HBV extends the usefulness of these reviews to the fundamental researcher. Most of the sections contain important information on other potential virus-encoded drug targets, and one chapter specifically addresses proteases as targets for the treatment of different picornaviral infections.Most chapters are highly informative and well written. Items such as vaccination, drug resistance, recombination and quasi-species are dealt with satisfactorily, justifying the ambition of this publication to provide more than just a snapshot of present advances. Very rarely, crucial points are omitted; for example, the fact that the treatment of influenza depends crucially on rapid diagnosis (within the first 48 h of infection), a fact that might severely compromise the use of neuraminidase inhibitors in practice, is not mentioned. The chapter on herpesviruses, while otherwise complete, lacks information about human herpesvirus 8 (HHV-8), the agent of Kaposi's sarcoma. A chapter on papilloma viruses or rotaviruses (one of the most important killers in the world) would have been good, which could well have replaced the section on HIV. Unfortunately, this section contains no introduction worth that name and deals with the sole development of protease inhibitors (concentrating on only one of them), and did not deserve to be included in this fine monography, which otherwise merits its place on the bookshelf of every virologist.