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.