The compound DATEM inhibits respiratory syncytial virus fusion activity with epithelial cells.
The effect of diacetyltartaric acid esters of mono and diglycerides (DATEM) on fusion of respiratory syncytial virus (RSV) with HEp-2 cells was studied using the R18 fluorescence dequenching fusion assay. At DATEM concentrations less than 2.0 microg/ml, the inhibition of fusion increased with the concentration of DATEM. At 2 microg/ml of DATEM, the fusion was suppressed by 80-90%. Studies examining possible mechanism of fusion-inhibition indicated that DATEM was likely adsorbed onto lipid membranes of both viral envelope and target cell membranes. Quantitative measurements of DATEM adsorption onto membranes were also performed using lipid monolayers and vesicles. The surface pressure of lipid monolayer formed at the air/aqueous interface increased as the concentration of DATEM in the monolayer subphase increased, suggesting that DATEM was inserted into the monolayer. As the concentration of DATEM in vesicle suspensions increased, electrophoretic mobility of initially uncharged lipid vesicles also increased, reflective of increased negative charge at vesicle surfaces. These results strongly suggest that the insertion of DATEM onto membranes inhibited viral fusion. DATEM may prove to be effective in limiting the infectivity of RSV by interference with the fusion of the viral envelope with target cell membranes.
Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
Shinpei
S
Ohki
Jin-Zhou
JZ
Liu
Joseph
J
Schaller
Robert C
RC
Welliver
D000327:Adsorption; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000821:virology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000648:ultrastructure / Q000821:virology; D015726:Giant Cells / Q000187:drug effects* / Q000821:virology; D005989:Glycerides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000502:physiology; D013644:Tartrates / Q000737:chemistry / Q000494:pharmacology*; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D005989:Glycerides; D013644:Tartrates