Apr 21, 2020

Inhibition of PIKfyve kinase prevents infection by EBOV and SARS-CoV-2

BioRxiv : the Preprint Server for Biology
Y.-L. KangTom Kirchhausen

Abstract

Virus entry is a multistep process. It initiates when the virus attaches to the host cell and ends when the viral contents reach the cytosol. Genetically unrelated viruses can subvert analogous subcellular mechanisms and use similar trafficking pathways for successful entry. Antiviral strategies targeting early steps of infection are therefore appealing, particularly when the probability for successful interference through a common step is highest. We describe here potent inhibitory effects on content release and infection by chimeric VSV containing the envelope proteins of EBOV (VSV-EBOV) or SARS-CoV-2 (VSV-SARS-CoV-2) elicited by Apilimod and Vacuolin-1, small molecule inhibitors of the main endosomal Phosphatidylinositol-3-Phosphate/Phosphatidylinositol 5-Kinase, PIKfyve. We also describe potent inhibition of SARS-CoV-2 strain 2019-nCoV/USA-WA1/2020 by Apilimod. These results define new tools for studying the intracellular trafficking of pathogens elicited by inhibition of PIKfyve kinase and suggest the potential for targeting this kinase in developing a small-molecule antiviral against SARS-CoV-2.

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Mentioned in this Paper

In Vivo
Doxycycline
CRISPR-Cas Systems
DNA-Directed RNA Polymerase
RNA Polymerase Assembly Pathway
methyl 1-thio-beta-D-galactopyranoside
Promoter
Thiogalactosides
Adverse Event
Human Cell Line

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