TY - JOUR T1 - Repurposing of Miglustat to inhibit the coronavirus Severe Acquired Respiratory Syndrome SARS-CoV-2 JF - bioRxiv DO - 10.1101/2020.05.18.101691 SP - 2020.05.18.101691 AU - Sreejith Rajasekharan AU - Rafaela Milan Bonotto AU - Yvette Kazungu AU - Lais Nascimento Alves AU - Monica Poggianella AU - Pamela Martinez Orellana AU - Natasa Skoko AU - Sulena Polez AU - Alessandro Marcello Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/18/2020.05.18.101691.abstract N2 - Repurposing clinically available drugs to treat the new coronavirus disease COVID-19 is an urgent need in these early stages of the SARS-CoV-2 pandemic, when very few treatment options are available. The iminosugar Miglustat is a well-characterized drug for the treatment of rare genetic lysosome storage diseases such as Gaucher and Niemann-Pick type C, and has also been described to be active against a variety of enveloped viruses. The activity of Miglustat is here demonstrated for SARS-CoV-2 at concentrations achievable in the plasma by current clinical regimens without cytotoxicity. The drug acts at the post-entry level and leads to a marked decrease of viral proteins and release of infectious virus. The mechanism resides in the inhibitory activity towards α-glucosidases that are involved in early stages of glycoprotein N-linked oligosaccharide processing in the endoplasmic reticulum, leading to a marked decrease of the viral Spike protein. The wealth of available data on the clinical use of Miglustat for the treatment of lysosomal storage disorders and the antiviral properties against SARS-CoV-2 make it an ideal candidate for drug repurposing.Competing Interest StatementThe authors have declared no competing interest. ER -