New publication in Scientific Reports: Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1

Dengue is a mosquito-borne disease caused by infection with the dengue virus (DENV), which remains a major
public health concern worldwide due to the lack of available specific treatments or antiviral drugs.
This study investigated the potential repurposing of domperidone, an antiemetic and gastrokinetic
agent, to control DENV infection. Domperidone was identified through pharmacophore-based virtual
screening as a small molecule capable of binding to both the viral envelope (E) and the nonstructural protein
1 (NS1) of DENV. Molecular dynamics (MD) simulations and surface plasmon resonance (SPR) analysis
were subsequently performed to determine specific interactions between domperidone and the DENV E and
NS1 proteins, as well as their binding affinity. Treatment of immortalized human hepatocyte-like cells (imHC)
with domperidone could inhibit DENV production and NS1 secretion in a dose-dependent manner
following infection with DENV serotype 2. These inhibitory effects were mediated by a reduction in viral
RNA replication and viral E and NS1 protein expression, but not by interfering with viral entry into
cells or NS1 oligomerization. The suppression of DENV production and NS1 secretion by domperidone
was observed across all four DENV serotypes to varying degrees among different virus strains. The
findings from our study suggest that domperidone could be repurposed based on its viral targets to modulate DENV.

Reference

Kaewjiw N, Thaingtamtanha T, Mehra D, Chawnawa W, Prommool T, Puttikhunt C, Songjaeng A, Kongmanas K, Avirutnan P, Luangaram P, Srisawat C, Roytrakul S, Bäurle SA, Noisakran S. Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1. Sci Rep. Jan. 30, 2025;15(1):3817. doi: 10.1038/s41598-025-87146-w