The PIKfyve Inhibitor Apilimod: A Double-Edged Sword against COVID-19

The PIKfyve inhibitor apilimod is currently undergoing clinical trials for treatment of COVID-19. However, although apilimod might prevent viral invasion by inhibiting host cell proteases, the same proteases are critical for antigen presentation leading to T cell activation and there is good evidenc...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2020-12, Vol.10 (1), p.30
Main Authors: Baranov, Maksim V, Bianchi, Frans, van den Bogaart, Geert
Format: Article
Language:English
Subjects:
Antigen presentation
Antigens
Antiviral Agents - adverse effects
Antiviral Agents - pharmacology
apilimod
Cell activation
Clinical trials
Coronaviruses
COVID-19
COVID-19 - drug therapy
COVID-19 - immunology
Cytokines
Dendritic cells
Disease transmission
Drugs
Humans
Hydrazones - adverse effects
Hydrazones - pharmacology
Immune system
Immunosuppression
Infections
Kinases
LAM-002A
Lymphocytes T
Medical research
Morpholines - adverse effects
Morpholines - pharmacology
Opinion
Peptide Hydrolases - metabolism
Phosphatidylinositol 3-Kinases - metabolism
Phosphoinositide-3 Kinase Inhibitors - adverse effects
Phosphoinositide-3 Kinase Inhibitors - pharmacology
PIKfyve
Protease Inhibitors - pharmacology
Proteins
Pyrimidines - adverse effects
Pyrimidines - pharmacology
SARS-CoV-2
SARS-CoV-2 - drug effects
Serine Endopeptidases - metabolism
Severe acute respiratory syndrome coronavirus 2
STA-5326
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Summary:The PIKfyve inhibitor apilimod is currently undergoing clinical trials for treatment of COVID-19. However, although apilimod might prevent viral invasion by inhibiting host cell proteases, the same proteases are critical for antigen presentation leading to T cell activation and there is good evidence from both in vitro studies and the clinic that apilimod blocks antiviral immune responses. We therefore warn that the immunosuppression observed in many COVID-19 patients might be aggravated by apilimod.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10010030