RT Journal Article
SR Electronic
T1 Targeting the endolysosomal host-SARS-CoV-2 interface by the clinically licensed antidepressant fluoxetine
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.27.222836
DO 10.1101/2020.07.27.222836
A1 Sebastian Schloer
A1 Linda Brunotte
A1 Jonas Goretzko
A1 Angeles Mecate-Zambrano
A1 Nadja Korthals
A1 Volker Gerke
A1 Stephan Ludwig
A1 Ursula Rescher
YR 2020
UL http://biorxiv.org/content/early/2020/07/27/2020.07.27.222836.abstract
AB The Corona Virus Disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Related Coronavirus 2 (SARS-CoV-2) is a global health emergency. As only very limited therapeutic options are clinically available, there is an urgent need for the rapid development of safe, effective, and globally available pharmaceuticals that inhibit SARS-CoV-2 entry and ameliorate COVID-19. In this study, we explored the use of small compounds acting on the homeostasis of the endolysosomal host-pathogen interface, to fight SARS-CoV-2 infection. We find that fluoxetine, a widely used antidepressant and a functional inhibitor of acid sphingomyelinase (FIASMA), efficiently inhibits the entry and propagation of SARS-CoV-2 in the cell culture model without cytotoxic effects. Mechanistically, fluoxetine induced both impaired endolysosomal acidification and the accumulation of cholesterol within the endosomes. As the FIASMA group consists of a large number of small compounds that are well-tolerated and widely used for a broad range of clinical applications, exploring these licensed pharmaceuticals may offer a variety of promising antivirals for host-directed therapy to counteract SARS-CoV-2 and COVID 19.Significance Only very limited therapeutic options are clinically available for treatment of Corona Virus Disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Related Coronavirus 2 (SARS-CoV-2), and the development of safe, effective, and globally available pharmaceuticals are urgently required. We report that the widely used antidepressant fluoxetine efficiently inhibits the early entry and propagation of SARS-CoV-2 in the cell culture model, and may offer a promising approach for host-directed therapy to counteract SARS-CoV-2 and COVID 19.Competing Interest StatementThe authors have declared no competing interest.