Dengue viral infection, caused by the Dengue virus, spreads to humans through the bite of infected mosquitoes and affects over half of the global population, with an estimated 500 million infections annually. Despite the urgent need, no effective treatment is currently available, though several candidates are in pre-clinical and clinical testing.
A major challenge in drug and vaccine development is the existence of four distinct serotypes, requiring any effective treatment to neutralize all serotypes equally. However, no pan-serotype-specific treatment currently exists, highlighting the need for novel drug-like compounds targeting all Dengue virus serotypes.
To address this, we employed virtual screening methodologies to identify compounds targeting domain III of the E glycoprotein, a crucial region involved in viral fusion with the host membrane and a key target of neutralizing antibodies. Our study screened 3 million compounds and identified two small molecules with consistent binding affinity across all four serotypes. These compounds exhibit favorable drug-like properties, making them promising candidates for further development as potential Dengue virus treatments.
Reference:
Agrawal, P., Arya, H., & Senthil Kumar, G. (2024). Structure-based identification of small-molecule inhibitors that target the DIII domain of the Dengue virus glycoprotein E pan-serotypically. PloS one, 19(10), e0311548. https://doi.org/10.1371/journal.pone.0311548