Antiviral drug discovery and development: where chemistry meets with biomedicine.
The successful development of antiviral drugs is highly dependent on a close interaction and collaboration between the chemist and the biologist (biomedic). This is illustrated by a number of representative examples: S-adenosylhomocysteine (SAH) hydrolase inhibitors which display broad-spectrum antiviral activity, bromovinyldeoxyuridine (BVDU) and derivatives thereof, that are highly selective inhibitors of varicella-zoster virus (VZV), (dideoxy)nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) which are now widely used in the treatment of HIV infections (AIDS), the bicyclams (i.e. AMD3100) which were originally discovered as anti-HIV agents, then found to be potent CXCR4 antagonists and now being pursued for a number of indications such as stem cell mobilization, and the acyclic nucleoside phosphonates which have heralded a new strategy for the treatment of various DNA virus (herpes-, adeno-, pox-, papillomavirus) infections (cidofovir), hepatitis B (adefovir) and AIDS (tenofovir).
De Clercq
Erik
E
Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. erik.declercq@rega.kuleuven.ac.be
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000145:classification / Q000493:pharmacokinetics / Q000494:pharmacology*; D004267:DNA Viruses / Q000187:drug effects*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006564:Herpesviridae / Q000187:drug effects; D006801:Humans; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012328:RNA Viruses / Q000187:drug effects*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D009705:Nucleosides