Abstract：
:Despite the importance of Dengue virus (DENV) infection in human health, there is not a fully effective vaccine or antiviral treatment against the infection. Since lipids such as cholesterol are required during DENV infection, its uptake and synthesis are increased in infected cells. Ezetimibe is an FDA-approved drug that reduces cholesterol uptake by inhibiting the endocytosis through Niemman-Pick C1-Like 1 (NPC1L1) receptor, expressed on the membrane of enterocytes and hepatocytes. Our results indicate that an increase in the amount of NPC1L1 occurs on the surface of Huh-7 cells during DENV infection, which correlates with an increase in cholesterol levels. Blockage of NPC1L1 with ezetimibe in concentrations up to 50 μM does not reduce cell viability but diminished total cellular cholesterol, the percentage of infected cells, viral yield, viral RNA and protein synthesis without affecting DENV binding and/or entry to Huh-7 cells. Moreover, ezetimibe inhibited DENV replicative complex formation and lipid droplets accumulation. All these results indicate that ezetimibe is an excellent drug to inhibit DENV infection and confirm that cholesterol is a key target to inhibit viral infection.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Osuna-Ramos JF,Reyes-Ruiz JM,Bautista-Carbajal P,Cervantes-Salazar M,Farfan-Morales CN,De Jesús-González LA,Hurtado-Monzón AM,Del Ángel RMdoi
10.1016/j.antiviral.2018.10.024subject
Has Abstractpub_date
2018-12-01 00:00:00pages
151-164eissn
0166-3542issn
1872-9096pii
S0166-3542(18)30322-Xjournal_volume
160pub_type
杂志文章abstract：:The 21st International Conference on Antiviral Research provided novel insights and approaches to drug discovery across a wide array of virologic fields. Topics ranged from the chemical synthesis of new compounds against the human immunodeficiency virus (HIV) to the long-term use of established drugs against influenza...
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