Dengue virus (DENV) is a mosquito-borne
flavivirus responsible for
dengue fever. Studies have shown that DENV interacts with metabolic pathways, in particular the
glycolysis is increased in DENV-infected cells. However, the dependence of DENV on this pathway has not been investigated in details. The inventors identified an interaction between the non-
structural protein 3 (NS3) of DENV and GCKR, a
host protein that regulates the liver-specific
hexokinase GCK. NS3 expression alone was found to increase glucose consumption and lactate
secretion in an hepatic
cell line expressing GCK. The inventors observed that GCKR interaction with GCK decreases DENV replication, supporting the role of NS3 as an inhibitor of GCKR function. By targeting NAD(H)
biosynthesis with the
antimetabolite 6-Amino-
Nicotinamide (6-AN), the inventors decreased cellular glycolytic activity and inhibited DENV replication in hepatic
cell. The present invention thus relates to the use of inhibitors of NAD
biosynthesis for the treatment of
dengue virus infections.