Abstract
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.
Keywords:
COVID-19; LAM-002A; PIKfyve; SARS-CoV-2; STA-5326; apilimod.
MeSH terms
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Antiviral Agents / adverse effects*
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Antiviral Agents / pharmacology
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COVID-19 / immunology
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COVID-19 Drug Treatment*
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Humans
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Hydrazones / adverse effects*
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Hydrazones / pharmacology
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Morpholines / adverse effects*
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Morpholines / pharmacology
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Peptide Hydrolases / metabolism
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphoinositide-3 Kinase Inhibitors / adverse effects*
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Phosphoinositide-3 Kinase Inhibitors / pharmacology
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Protease Inhibitors / pharmacology
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Pyrimidines / adverse effects*
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Pyrimidines / pharmacology
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SARS-CoV-2 / drug effects*
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Serine Endopeptidases / metabolism
Substances
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Antiviral Agents
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Hydrazones
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Morpholines
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Peptide Hydrolases
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Phosphatidylinositol 3-Kinases
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Phosphoinositide-3 Kinase Inhibitors
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Protease Inhibitors
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Pyrimidines
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Serine Endopeptidases
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PIKFYVE protein, human
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apilimod
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TMPRSS2 protein, human