Biophysical effects of melatonin and azithromycin on model pulmonary membranes

Pulmonary cell membranes are the first line of defense against respiratory viral infections, including the recent coronavirus (SARS-COV-2). Common drugs, e.g. azithromycin and melatonin, have shown promise as agents in slowing down and ameliorating the symptoms of respiratory viral infections. The generic effects of these drugs, across a range of viral infections, suggest an indirect mechanism by which they inhibit viral activity – plausibly by altering membrane biophysical properties. Here, we report experimental results on the structural and mechanical effects of azithromycin and melatonin on model pulmonary membranes. Surface pressure-area isotherms of Langmuir monolayers show that both drugs increase lipid packing and decrease the monolayer compressibility at physiologically relevant surface pressures. Complementary differential scanning calorimetry (DSC) measurements support these results and indicate an increase in the transition temperature upon the inclusion of the drug molecules. Our observations are consistent with previous studies reporting on melatonin induced stabilization of lateral lipid domains. Further measurements using Brewster-angle microscopy and neutron reflectometry illustrate how the inclusion of the drug molecules influences lateral membrane organization.