Antiviral Methods And Protocols

Changing Methods for Discovering Antiviral Drugs 1 1 Changing Methods for Discovering Antiviral Drugs Philip S. Jones 1. Introduction Viral diseases were largely untreatable 40 yr ago. Now effective and safe therapies are available. This has led to significant improvements in the quality of life for large numbers of patients. New viral diseases are, however, continuing to emerge and established viruses have been shown to develop resistance to available therapies making this a fertile area for continued drug discovery. The processes used to discover drugs have also changed enormously over the past 40 yr. Nowhere have these changes been more apparent than in the field of antiviral therapy. Therefore, the development of antiviral drugs makes an excellent example for documenting the changes in approaches used to discover active agents. This brief chapter describes some of these changes—from the broad screening in animals and tissue culture first used to the mechanism–based approaches using computer assisted techniques and biostructural information. 2. Beginnings The origins of antiviral therapies can be traced to the early 1950s, when sulfonamide antibiotics were tested for activity against poxviruses using mice infected with vaccinia (1). A decade of work at the Wellcome laboratories culminated in the development of methisazone, which was introduced in 1960 for the prophylaxis of smallpox (see Scheme 1). Notable success in the smallpox epidemic in Madras in 1963 demonstrated the value of this compound, but vacci