Effects of singlet oxygen generated by JL103 viral fusion inhibitor on membrane nanoarchitecture

HOLLMANN A; GONÇALVES S; AUGUSTO, MT; CASTANHO, MA; LEE B; SANTOS, NC

Dresden

Congreso; 10th European Biophysics Congress; 2015

European Biophysical Societies

Recently, broad-spectrum small-molecule antiviral drug were described, preventing enveloped virus entry at an intermediate step, after virus binding but before virus?cell fusion. Those compounds, including an oxazolidine-2,4-dithione derivates named JL103, which presented the most promissing results, act deleteriously on the virus envelope but not at the cell membrane level [Vigant et al (2013) PLoS Pathog. 9:e1003297; Hollmann et al (2014) Biochem J. 459:161]. In this work, by using AFM, we aimed at unraveling the effects that JL103 is able to induce in the lipid membrane architecture at the nanoscale [Hollmann et al (in press) Nanomedicine]. Our results indicate that singlet oxygen produced by JL103 decreases membrane thickness, with and expansion of the area per phospholipid, by attacking the double bonds of unsaturated phospho-lipids. In terms of antiviral activity, it is well-known that the physical state of the lipid bilayer has a major influence on membrane fusion process. We demonstrated that JL103 is able to remodel membrane nanoarchitecture, leading that the viral membrane may lose its ability to undergo the extreme membrane curvature transitions necessary for the fusion, resulting in viral entry inhibition.