In search of a selective therapy of viral infections

This article is meant as an introductory chapter to the special issue of Antiviral Research on "Twenty-five years of antiretroviral drug development: progress and prospects", commemorating the first description of azidothymidine (AZT) as an antiretroviral agent. This has prompted me to highlight some of the hallmarks that played an important role in my own search of a selective therapy of viral infections: i.e., the induction of interferon by double-stranded RNA [such as poly(I).poly(C)], allowing the cloning and expression of beta-interferon; the discovery of the reverse transcriptase (RT) (and HIV as a retrovirus depending for its replication on RT), allowing the identification and development of a wide variety of RT inhibitors, nowadays used for the treatment of AIDS; the specificity of herpesvirus inhibitors such as acyclovir and BVDU, in the treatment of HSV and VZV infections; the role of acyclic nucleoside phosphonates (tenofovir, adefovir and cidofovir) in the treatment of HIV, HBV and DNA virus infections; and that of the NNRTIs (leading from TIBO to rilpivirine) as an essential part of the current anti-HIV drug cocktails. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010.