Vacuole

Endosome

Pathology

Virus

Disease

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Biology

Viral envelope

Lipid bilayer fusion

Viral replication

Cytoplasm

Virology

Ebola virus

Coronavirus

Ebolavirus

Vesicular stomatitis virus

Cell biology

Viral entry

Medicine

Intracellular

Proceedings of the National Academy of Sciences

Significance The membrane fusion proteins of viral pathogens as diverse in their replication strategies as coronaviruses and filoviruses depend, for their functional activity, on proteolytic processing during cell entry. Endosomal cathepsins carry out the cleavages. We have constructed chimeric forms of vesicular stomatitis virus (VSV) bearing the fusion proteins of Zaire ebolavirus (ZEBOV) or SARS coronavirus 2 (SARS-CoV-2) and shown that two small-molecule inhibitors of an endosomal lipid kinase (PIKfyve) inhibit viral infection by preventing release of the viral contents from endosomes. Both inhibitory compounds cause distension of Rab5 and Rab7 subcompartments into small vacuoles. One of them (Apilimod) also inhibits infection of cells by authentic SARS-CoV-2. The results point to possibilities for host targets of antiviral drugs.

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