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1.
Antiviral Res ; 199: 105267, 2022 03.
Article in English | MEDLINE | ID: mdl-35227759

ABSTRACT

The central role of Ebola virus (EBOV) VP40 in nascent virion assembly and budding from infected host cells makes it an important therapeutic target. The mechanism of dimerization, following oligomerization of VP40 leading to the production of virus-like particles (VLP) has never been investigated for the development of therapeutic candidates against Ebola disease. Molecular dynamics-based computational screening targeted VP40 dimer with 40,000,000 compounds selected 374 compounds. A novel in vitro screening assay selected two compounds, NUSU#1 and NUSU#2. Conventional VLP assays consistently showed that both compounds inhibited EBOV VP40-mediated VLP production. Intriguingly, NUSU#1 inhibited the VP40-mediated VLP production in other ebolavirus species and the Marburg virus, but did not inhibit Lassa virus Z-mediated VLP production. These results strongly suggested that the selected compounds are potential lead drug candidates against Filovirus disease via disruption of VP40-mediated particle production.


Subject(s)
Ebolavirus , Hemorrhagic Fever, Ebola , Marburgvirus , Ebolavirus/chemistry , Humans , Viral Matrix Proteins/chemistry , Virus Release
2.
Lipids Health Dis ; 9: 77, 2010 Jul 24.
Article in English | MEDLINE | ID: mdl-20653972

ABSTRACT

BACKGROUND: Dietary 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol (BOO) has been reported to inhibit pancreatic lipase activity in vitro and suppress postprandial hypertriacylglycerolemia in humans. In the present study, the anti-obesity activities of BOO and its inhibitory effects on lymphatic triacylglycerol (TAG) absorption were investigated in rats. METHODS: In Experiment 1, rats were fed either BOO or soybean oil (SO) diet for 6 weeks. In the BOO diet, 20% of SO was replaced with an experimental oil rich in BOO. In Experiments 2 and 3, rats cannulated in the thoracic duct were administered an emulsions containing trioleoylglycerol (OOO) or an oil mixture (OOO:BOO, 9:1). Tri[1-14C]oleoylglycerol (14C-OOO) was added to the emulsions administered in Experiment 3. RESULTS: No observable differences were detected in food intake or body weight gain between the BOO and SO groups in Experiment 1. Plasma and liver TAG concentrations and visceral fat weights were significantly lower in the BOO group than in the SO group. The apparent absorption rate of fat was significantly lower in the BOO group than in the SO group. In Experiment 2, the lymphatic recovery of oleic and behenic acids was significantly lower at 5 and 6 h after BOO administration than after OOO administration. In Experiment 3, the lymphatic recovery of 14C-OOO was significantly lower at 5 and 6 h after BOO administration than after OOO administration. CONCLUSIONS: These results suggest that BOO prevents deposition of visceral fat and hepatic TAG by lowering and delaying intestinal absorption of TAG.


Subject(s)
Anti-Obesity Agents/therapeutic use , Fatty Acids , Intestinal Absorption , Obesity/prevention & control , Oleic Acid , Triglycerides/metabolism , Triglycerides/therapeutic use , Animals , Anti-Obesity Agents/chemical synthesis , Cholesterol/blood , Cholesterol/metabolism , Eating , Fat Substitutes/chemical synthesis , Fat Substitutes/therapeutic use , Fatty Acids/metabolism , Feces/chemistry , Hypertriglyceridemia/blood , Hypertriglyceridemia/prevention & control , Intra-Abdominal Fat/pathology , Kinetics , Liver/metabolism , Liver/pathology , Lymph/metabolism , Lymphatic System/physiology , Male , Obesity/blood , Obesity/diet therapy , Obesity/pathology , Oleic Acid/metabolism , Organ Size , Rats , Rats, Wistar , Triglycerides/blood , Triglycerides/chemical synthesis , Weight Gain
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