Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Poster Abstracts

7-POS Board 2 DO ANTIDEPRESSANTS MODULATE BIOLOGICAL MEMBRANES? Beatrix L Goggin 1,2 ; Jane R Allison 1 ; Oleg O Glebov 3,4 ; 1 University of Auckland, School of Biological Sciences, Auckland, New Zealand 2 University of Auckland, School of Chemical Sciences, Auckland, New Zealand 3 Qingdao University, Institute of Neuroregeneration and Neurorehabilitation, Qingdao, China 4 King's College London, Department of Old Age Psychiatry, London, United Kingdom SARS-CoV-2 has been a pervasive threat to global health since its emergence in December 2019. The unprecedented need for rapid and readily available treatments and prophylactics coupled to the initial lack of information on the virus itself lead many researchers to turn to drug repurposing in favour of de novo drug development. Initial results identified 11 existing drugs that may block endocytic pathways facilitating SARS-CoV-2 entry into cells. Further work revealed that the antidepressant (AD) Fluvoxamine may cause rapid and significant modulation of endocytosis at even sub-therapeutic concentrations. Given the ubiquitous prescription and assumed safety of ADs, they prove a highly attractive candidate as a prophylactic for SARS CoV-2 or similar viruses that may emerge in the future. The widespread use of ADs also makes the discovery of unexpected off-target effects of significant interest for further investigation. Though these drugs are highly prescribed, relatively little is known about their exact mechanism of action or cause behind side effect profiles. Molecular dynamics simulations allow for investigation of interactions of ADs with membranes of varying compositions as models for different body tissues. The preliminary work reported here was carried out with a selection of ADs, including Fluvoxamine, and a model blood-brain barrier membrane. As AD action is generally considered in a central nervous system context, the blood-brain barrier proves a cogent choice as the first membrane type with which to investigate AD interaction. These results will inform direction of future in vitro and computational research, including expanding the range of drugs tested and construction of additional membrane models (such as the gut epithelium). This research is hoped to aid elucidation of the mechanism of potential prophylactic effect of ADs against SARS-CoV-2, as well as improve insight into the mechanism of action of ADs for their intended use.

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