Periodic Reporting for period 1 - LIsTEN (β-Lactams as flaviviral NS3 protease inhibitors)
Période du rapport: 2017-05-02 au 2019-05-01
Currently, no therapeutics against dengue, West Nile or Zika virus are available on the market and the treatment remains symptomatic. A first dengue vaccine which has been recently released has shown moderate efficacy, whereas the development of chemical agents is still in preclinical stage. Hence, urgent need for drugs against flaviviruses is apparent.
This project was aimed at investigating β-lactams as pharmaceutical agents against flaviviruses, with the focus on dengue and West Nile virus. The target of β-lactam compounds planned in this project was flaviviral NS3 protease. NS3 protease is a valuable pharmacological target as its activity is necessary for virus replication. On the other hand, β-lactams are most well known as very potent antibiotics. Antibacterial activity of β-lactams is based on their ability to inhibit bacterial transpeptidase, an enzyme crucial for the bacterial cell wall synthesis. Due to structural and functional similarities between flaviviral NS3 protease and bacterial transpeptidase, it is reasonable to assume that β-lactams might represent a valuable group of compounds in the development of antiflaviviral drugs. The objective of this project was to investigate β-lactams as inhibitors of NS3 protease and potential antiflaviviral drugs.