Background

Dengue virus (DENV) in one of four serotypes is the cause of dengue fever. All four serotypes (DENV-1 to 4) can cause the full spectrum of disease.

Dengue is the most rapidly spreading mosquito-borne viral disease in the world. In the last 50 years, incidence has increased 30-fold.

Immunization against one of the serotypes does not immunize against the 3 other ones.

An estimated 50-100 million dengue infections occur annually and approximately 2.5 billion people live in dengue endemic countries (more than 110 endemic countries).

-> The infection kills about 30 000 persons each year and to date, no antiviral treatment nor vaccine is available.

KEY Benefits vs. STATE OF THE ART

• The hit compounds are non-nucleoside inhibitors (NNIs) active on a druggabletarget (RNA-dependent RNA polymerase (RdRP) NS5 protein).
• This drug family is active against the 4 serotypes of DENV.
• Some of these compounds demonstrated activity against other flaviviruses: WNV, YFV, KUNV (in vitro polymerase cell-free assay).

Development status

• Screening platform: more than 17,000 compounds evaluated
• In vitro testing on RNA-dependent RNA polymerase (RdRP) NS5 protein of 4 serotypes of DENV
• Better EC50 among the drug family = 12nM on DENV2
• Lead optimization on going

Applications

Treatment of flavivirus infections:

• Dengue Virus (in severe and lethal dengue hemorrhagic fevers),
• West Nile Virus,
• Yellow Fever Virus,
• Kunjin Virus,
• Japanese Encephalitis Virus ,
• ...