The development of a pan serotype active NS4B inhibitor against dengue virus

We propose to develop an antiviral drug to treat dengue virus infection. Uncomplicated dengue fever is associated with significant morbidity, including debilitating pain. Severe forms of the disease are life threatening, leading to approximately 22,000 deaths each year. No antiviral drug has yet been developed. Recent advances with novel dengue vaccines are now compromised with the observed increased risk of severe disease in naive children. As dengue vaccine public health impact continues to be assessed, an effective oral drug will be much needed for the successful treatment of dengue. Dengue epidemiology studies have shown that viremia is higher in severe dengue patients compared to those with dengue fever (1). Therefore, a specific antiviral given early in the infection that can effectively lower the viral load may significantly improve disease outcome. An appropriate compound may also be useful for seasonal prophylaxis. Novartis Institute for Tropical Diseases has identified ME-78-OH90 as the most potent dengue inhibitor reported to date, with a promising preliminary safety profile. With the strong drug development expertise at Novartis and the support of Wellcome Trust for key preclinical experiments, we will be able to advance this candidate to clinical trials.