Identification of a broad-spectrum flavivirus inhibitor targeting NS2A, a previously unidentified target
Year: 2025
Type: preprint
Abstract: Flaviviruses, such as dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), Japanese encephalitis virus (JEV), and yellow fever virus (YFV), constitute a significant public health concern with billions of people at risk of infection. Climate change and the expanding geographical distribution of mosquito vectors transmitting flaviviruses have increased their potential to cause large-scale disease outbreaks. The frequency and severity of disease outbreaks highlights the urgent need for a broad-spectrum antiviral agent targeting flaviviruses. In this work, we conducted a comprehensive morphological profiling of approximately 200,000 small molecules through a fluorescence-based high-content imaging platform, which led to the identification of a singular small molecule exhibiting broad-spectrum activity against flaviviruses. Subsequent hit deconvolution against DENV serotype 2 (DENV-2) revealed NS2A as a novel therapeutic target and suggested a mechanism whereby the identified small molecule inhibits the interaction between NS2A and the prM protein, revealing a previously uncharacterized antiviral mechanism of action.
Source: Research Square
Authors: Olivia Goethals, Doortje Borrenberghs, Kitti Wing Ki Chan, Sven Van Brandt, Steffen Jaensch, Milly Choy, Peggy Geluykens, Asmae El Bouayadi, Dax Lauwers, Pradeep Bist, Bart Stoops, Jeroen Van de Ven, Peter Vermeulen, Sarah Megens, Danielle Peeters, Suzanne Kaptein, Johan Neyts, Subhash Vasudevan, Anil Koul
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4407837244