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Updated: May 26, 2026
Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds
Published on: October 29, 2015
U18666A, an intra-cellular cholesterol transport inhibitor, inhibits dengue virus entry and replication
Mee Kian Poh1, Guanghou Shui, Xuping Xie
1Dengue Unit, Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos #05-01, Singapore 138670, Singapore.
Abstract:
The level of cholesterol in host cells has been shown to affect viral infection. However, it is still not understood why this level of regulation is important for successful infection. We have shown in this study that dengue virus infection was affected when the cholesterol intake in infected cells was disrupted using a cholesterol transport inhibitor, U18666A. The antiviral effect was found to result from two events: retarded viral trafficking in the cholesterol-loaded late endosomes/lysosomes and suppressed de novo sterol biosynthesis in treated infected cells. We also observed an additive antiviral effect of U18666A with C75, a fatty acid synthase inhibitor, suggesting dengue virus relies on both the host cholesterol and fatty acid biosynthesis for successful replication.
Insights
Disrupting host cell cholesterol levels with U18666A inhibits dengue virus infection by slowing viral transport and suppressing sterol synthesis. This suggests dengue virus replication depends on host cholesterol and fatty acid biosynthesis.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Host cell cholesterol levels are known to influence viral infections.
- The precise mechanisms by which cholesterol impacts viral replication remain incompletely understood.
Purpose of the Study:
- To investigate the role of host cell cholesterol regulation in dengue virus infection.
- To elucidate the molecular mechanisms underlying the antiviral effects of cholesterol modulation.
Main Methods:
- Utilized the cholesterol transport inhibitor U18666A to disrupt cholesterol homeostasis in infected cells.
- Assessed viral trafficking and sterol biosynthesis pathways.
- Investigated the combined effects of U18666A with C75, a fatty acid synthase inhibitor.
Main Results:
- U18666A treatment significantly affected dengue virus infection.
- Antiviral effects were attributed to retarded viral trafficking in cholesterol-loaded late endosomes/lysosomes.
- Suppressed de novo sterol biosynthesis was observed in treated infected cells.
- An additive antiviral effect was noted when U18666A was combined with C75.
Conclusions:
- Dengue virus replication is significantly impacted by host cell cholesterol levels.
- Cholesterol homeostasis is crucial for efficient viral trafficking and biosynthesis.
- Dengue virus relies on both host cholesterol and fatty acid biosynthesis for successful replication, presenting potential therapeutic targets.
