Abstract
Dengue Fever, a widespread mosquito-borne disease caused by the dengue virus (DENV), poses a major health threat in tropical and subtropical regions worldwide, resulting in millions of infections yearly. Severe cases of dengue fever have a mortality rate of around fifteen percent. Currently, there are no antiviral treatments for this disease and the only FDA-approved vaccine has been known to have adverse effects, especially in children. Thus, there is an urgent need for new therapeutics for Dengue fever. The largest issue with developing an antiviral treatment is that DENV has four serotypes that each differ slightly enough to pose problems with one compound inhibiting all four. This study addresses that challenge to some extent by focusing on in silico screening of potential hits targeting the envelope glycoprotein, which is relatively conserved across these four serotypes. Using pharmacophore screening and in silico evaluation of ligands, we identified compounds which could potentially have high affinity to the envelope glycoprotein for two of the four DENV serotypes. These in silico results were validated experimentally using bio-layer interferometry. These findings lay a foundation for in vitro analysis and hit-to-lead studies, advancing the development of antivirals that can inhibit multiple serotypes of the dengue virus.