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Updated: Jul 10, 2026
Immunofluorescence to Monitor the Cellular Uptake of Human Lactoferrin and its Associated Antiviral Activity Against the Hepatitis C Virus
Published on: October 1, 2015
Anti-dengue activity of a cellular lipid uptake inhibitor, lipofermata
Songkran Thongon1, Chompunuch Boonarkart2,3, Thanyaporn Sirihongthong2,3
1Graduate Program in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, Thailand.
Abstract:
There is still no effective antiviral drug for Dengue virus (DENV). Fatty acid (FA) was previously shown to be essential for DENV replication. The availability of intracellular FA depends on both intracellular synthesis and uptake from extracellular sources. While inhibition of FA synthesis has been shown to hinder DENV replication, less is known about inhibition of cellular FA uptake. Fatty acid transporter isoform 2 (FATP2) is known to be highly expressed in hepatocyte, the major target cell of DENV. An immortalized hepatocyte-like cell line (imHC) was used to determine anti-DENV2 activity and FA uptake inhibitory function of Lipofermata (FATP2 inhibitor). FATP2 protein expression level was measured in DENV2-infected cell by western blotting. Finally, Synergistic effect of combination of Lipofermata and Orlistat (FA synthesis inhibitor) was evaluated. Lipofermata could inhibit DENV1 and DENV2 with a 50% inhibitory concentration (IC50) of 1.75 and 1.74 µM, respectively with a similar selectivity index of 3.4. FATP2 expression level was significantly upregulated by DENV2 infection. A combination of Lipofermata with Orlistat, a FA synthesis inhibitor, showed additive or synergistic inhibitory effects on DENV2 in drug synergy prediction models. Cellular FA uptake is therefore a promising target for new anti-DENV drug development.
Insights
New research shows inhibiting fatty acid uptake can fight Dengue virus (DENV). Lipofermata, a fatty acid transporter inhibitor, effectively reduced DENV replication in liver cells, suggesting a new drug development target.
Area of Science:
- Virology
- Drug Discovery
- Biochemistry
Background:
- Dengue virus (DENV) lacks effective antiviral treatments.
- Fatty acid (FA) metabolism is crucial for DENV replication.
- Cellular uptake of extracellular FA is a potential therapeutic target, distinct from FA synthesis inhibition.
Purpose of the Study:
- To investigate the anti-DENV activity of Lipofermata, a fatty acid transporter isoform 2 (FATP2) inhibitor.
- To assess the role of FATP2 in DENV infection.
- To evaluate the synergistic effect of Lipofermata combined with a FA synthesis inhibitor.
Main Methods:
- Utilized an immortalized hepatocyte-like cell line (imHC) for anti-DENV2 assays.
- Measured FATP2 protein expression via western blotting in DENV2-infected cells.
- Employed drug synergy prediction models to evaluate combined Lipofermata and Orlistat effects.
Main Results:
- Lipofermata demonstrated significant inhibition against DENV1 and DENV2 (IC50 ≈ 1.75 µM) with a selectivity index of 3.4.
- DENV2 infection led to a significant upregulation of FATP2 protein expression.
- Combination therapy with Lipofermata and Orlistat (FA synthesis inhibitor) exhibited additive or synergistic effects against DENV2.
Conclusions:
- Inhibition of cellular fatty acid uptake via FATP2 presents a promising strategy for novel anti-DENV drug development.
- Targeting FATP2 offers a new avenue for antiviral therapies against Dengue virus.
- Combined inhibition of FA uptake and synthesis may enhance therapeutic efficacy.
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