PT  - JOURNAL ARTICLE
AU  - Yuan-Lin Kang
AU  - Yi-Ying Chou
AU  - Paul W. Rothlauf
AU  - Zhuoming Liu
AU  - Timothy K. Soh
AU  - David Cureton
AU  - James Brett Case
AU  - Rita E. Chen
AU  - Michael S. Diamond
AU  - Sean P. J. Whelan
AU  - Tom Kirchhausen
TI  - Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2
AID  - 10.1101/2020.04.21.053058
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.21.053058
4099  - http://biorxiv.org/content/early/2020/06/15/2020.04.21.053058.short
4100  - http://biorxiv.org/content/early/2020/06/15/2020.04.21.053058.full
AB  - 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 Zaire ebolavirus (VSV-ZEBOV) 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 small-molecule antivirals against SARS-CoV-2.Competing Interest StatementM.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and on the Scientific Advisory Board of Moderna. The Diamond laboratory at Washington University School of Medicine has received sponsored research agreements from Moderna and Emergent BioSolutions.