A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

My search for a selective antiviral chemotherapy started more than 40 years ago with interferon inducers, then shifted to nucleoside analogs with the discovery of BVDU (brivudin), a highly selective anti-HSV-1 and anti-VZV agent, and to dideoxynucleoside analogs such as d4T (stavudine), anti-HIV agents. The search culminated in the discovery of acyclic nucleoside phosphonates (ANPs) (in collaboration with Antonin Holý), a key class of compounds active against HIV, hepatitis B virus, and DNA viruses at large; the best known of these compounds is tenofovir. Along the way, the principle of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) was established. This work, initiated in collaboration with the late Paul A.J. Janssen, eventually led to the identification of rilpivirine as perhaps an "ideal" NNRTI.