Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication.

BioRxiv : the Preprint Server for Biology
J. A. SilvasChristopher F. Basler

Abstract

Therapeutics targeting replication of SARS coronavirus 2 (SARS-CoV-2) are urgently needed. Coronaviruses rely on host membranes for entry, establishment of replication centers and egress. Compounds targeting cellular membrane biology and lipid biosynthetic pathways have previously shown promise as antivirals and are actively being pursued as treatments for other conditions. Here, we tested small molecule inhibitors that target membrane dynamics or lipid metabolism. Included were inhibitors of the PI3 kinase VPS34, which functions in autophagy, endocytosis and other processes; Orlistat, an inhibitor of lipases and fatty acid synthetase, is approved by the FDA as a treatment for obesity; and Triacsin C which inhibits long chain fatty acyl-CoA synthetases. VPS34 inhibitors, Orlistat and Triacsin C inhibited virus growth in Vero E6 cells and in the human airway epithelial cell line Calu-3, acting at a post-entry step in the virus replication cycle. Of these the VPS34 inhibitors exhibit the most potent activity.

Citations

Oct 30, 2020·International Journal of Molecular Sciences·Alexandra P M ClohertyFrançois Jean
Dec 17, 2020·Cells·Blanca Estela García-PérezNayeli Shantal Castrejón-Jiménez
Jun 3, 2021·Cells·Maimoona Shahid BhuttaRonen Borenstein
Jun 8, 2021·Frontiers in Microbiology·Keke WuJinding Chen

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Methods Mentioned

BETA
confocal microscopy

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