A 40-year journey in search of selective antiviral chemotherapy

Annu Rev Pharmacol Toxicol. 2011:51:1-24. doi: 10.1146/annurev-pharmtox-010510-100228.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-HIV Agents / pharmacology
  • Antiviral Agents / pharmacology*
  • Drug Design*
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • Humans
  • Interferon Inducers / pharmacology
  • Virus Diseases / drug therapy*
  • Virus Diseases / virology

Substances

  • Anti-HIV Agents
  • Antiviral Agents
  • Interferon Inducers