Inhibitors of Influenza Virus Neuraminidase and Endonuclease

Abstract

Abstract: Influenza virus infection is considered to be one of the most common, yet serious respiratory infections in terms of morbidity and mortality. Currently available medications are limited. Amantadine and Rimantidine are only partially successful in treating. influenza A infection, and have no effect against influenza B viruses. Vaccination shows some success but meets with the difficulties of predicting the highly variable mutated strains in the forthcoming epidemic season. Recently, there has been extensive research efforts focuse on the areas of inhibitors of influenza virus •neuraminidase and endonuclease. With detail understanding of the structural biology of influenza virus neuraminidase, Glaxo-Welcome's GG167 became the first potent neurami­ nidase inhibito which showed chemotherapeutic and chemoprophylactic effects in early human clinical trials. GGS4071, from Gilead Pharmaceutical, also demonstrated equivalent in vitro and invivo activities asGG I 67. GS4104, the ester pro-drug of GS4071 has good oral bioavailabilities in the animal assays. Along with the rapid developments in the area of neuraminidase inhibitors, cap-dependent endonuclease inhibitors which target the transcription of influenza virus mRNA are of great interest. The cap-dependent endonuclease seems to be unique to influenza virus with no cellular counterpart. The recent progress in the development of inhibitors of influenza neuraminidase and endonuclease are discussed in this review.