In vitro characterization of surfactin natural variants interaction with membranes, using liposomes as biomimetic models

Abstract

The SARS-Cov-2 covid-19 pandemic outbreak continues to claim victims to this day. As the vaccine is ineffective for completely eradicating the virus, there is an urgent need to look at other solutions, including developing antivirals. Lipopeptides, particularly surfactin, have been recognized for their antiviral activity against several enveloped viruses. However, a better comprehension of their mode of action is necessary to develop antivirals based on those lipopeptides. Moreover, studying several variants allows a better insight into the relationships between the structure of lipopeptides and their antiviral activity. In this work, a biophysical approach involving the use of liposomes as membrane biomimetic models was used. Four liposome models were created, including one aiming to mimic the host cell plasma membrane and one seeking to mimic the viral membrane. The effect of surfactin variants on membrane permeability and fluidity was analyzed on these biomimetic liposomes. Several mechanisms have been suggested to explain the surfactins action on liposomes. It was hypothesized that some variants had two-stage effects on membranes incorporating lipids such as cholesterol and PE. These lipids, potentially at the origin of this biphasic mechanism, could make the membrane more resistant to high surfactin concentrations. It was also hypothesized that the structure of some variants might influence the toxicity of surfactins on the membranes. Finally, it was observed that the studied variants might be more toxic on biological mimicking membranes than viral ones. Further studies are nevertheless mandatory to assert all these hypotheses.