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

Abstract

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.

Cited by papers we hold 9

• Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy · 2021
  No notice
• Perspectives and potential approaches for targeting neuropilin 1 in SARS-CoV-2 infection · 2021
  Not checked
• Endomembrane Tension and Trafficking · 2021
  Not checked
• SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis · 2021
  No notice
• SARS-CoV-2 requires cholesterol for viral entry and pathological syncytia formation · 2021
  No notice
• A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research · 2021
  No notice
• Structural basis for VPS34 kinase activation by Rab1 and Rab5 on membranes · 2021
  No notice
• SARS-CoV-2 tropism, entry, replication, and propagation: Considerations for drug discovery and development · 2021
  No notice
• Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion · 2020
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.