Posted by Among 19 CD derivatives studied, pretreatment of viral particles with DMA-β-CyD significantly reduced infectivity (by 2.25–2.67 log₁₀ units after 180 min of treatment) without affecting spike protein-ACE2 binding. DMA-β-CyD attenuated the procoagulant activity mediated by virion-associated aminophospholipids via interaction with the viral envelope. This effect was suppressed by 1-adamantanecarboxylic acid, suggesting that the inclusion of the target molecule of DMA-β-CyD is involved. Furthermore, DMA-β-CyD disrupted SARS-CoV-2 particles and reduced entry efficiency. Although the Japanese encephalitis virus (JEV)-associated procoagulant activity was weaker than the SARS-CoV-2-associated procoagulant activity at 37°C, DMA-β-CyD recognized virion-associated aminophospholipids exposed on the surface of JEV particles. Against JEV, DMA-β-CyD exhibited comparable antiviral activity (IC50 = 0.84 mM, CC50 ≥ 100 mM, SI ≥119). These findings demonstrate that DMA-β-CyD exerts antiviral effects against both SARS-CoV-2 and JEV by targeting envelope aminophospholipids, which supports lipid-targeting strategies as a promising basis for broad-spectrum antiviral development.
In this study, we demonstrate that DMA-β-CyD is the first compound shown to reduce the infectivity of SARS-CoV-2 and Japanese encephalitis virus (JEV) particles by interacting with aminophospholipids, such as phosphatidylserine (PS). By exploiting differences in lipid composition between viral envelopes and host cell membranes, DMA-β-CyD provides a novel, lipid-targeting antiviral mechanism and may serve as a valuable platform for addressing infections caused by emerging and drug-resistant viral pathogens.
Kusakari D, Kishimoto N, Oshiro K, Udeda Y, Takamune N, Motoyama K, Misumi S. Targeting envelope lipids with 2,6‑di‑O‑methyl‑3‑acetyl‑β‑cyclodextrin impairs infectivity of SARS‑CoV‑2 and Japanese encephalitis virus. J Virol. 2025 Dec 23;99(12):e0135725. doi: https://doi.org/10.1128/jvi.01357-25.