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. 2021 Jul 12;10(7):1761. doi: 10.3390/cells10071761

Table 2.

Potential medications for COVID-19-associated cytokine storms through targeting of MCs.

Medication Mechanism of Action References and Clinical Trials
Mast cell stabilizers
Cromolyn sodium
  • -

    Known as a MC stabilizer (based on rat MC studies) and act as a G-protein-coupled receptor 35 (GPR35) agonist

  • -

    Inhibits protein kinase C and chloride transport into MCs

  • -

    Blocks macrophages, the release of eicosanoids and cytokines, and the expression of adhesion molecules

  • -

    Regulates the expression of IL-6, TNF-α, TLR3, and TRIF

  • -

    Inhibits Nsp12

  • -

    Directly affects chloride and calcium ion channels

 [93,96,97,98,99,100]
Ketotifen
  • -

    Antagonizes the histamine-1 receptor

  • -

    Decreases lung lesions and apoptosis in the early stages of H5N1 infection

 [101,102]
Flavonoids
  • -

    Suppresses the release of histamine, leukotrienes, PGF2, and GM-CSF

  • -

    Targets virus entry into the host cells

  • -

    Reduces the expression of TNF-α, IL-1β, IL-6, and IL-8 by MC

  • -

    Constrains SARS-CoV serine proteases

  • -

    Downregulates histidine decarboxylase in MCs

  • -

    Inhibits MC degranulation and phosphorylation of some cell signaling proteins

 [103,104,105,106,107,108,109,110,111,112]
NCT04680819, NCT04468139, NCT04487964, NCT04622865
Coumarins
  • -

    Decreases TNF-α and IL-6 secretion

  • -

    Suppresses the phosphorylation of some MC signaling molecules

 [113,114,115]
Terpenoids
  • -

    Inhibits antigen-IgE-induced degranulation

 [116]
NCT04487964
Alkaloids
  • -

    Inhibits MC degranulation.

  • -

    Diminishes the synthesis of IL-4, IL-1, IL-6, and TNF-α.

  • -

    Prevents phosphorylation of signaling molecules

  • -

    Hinders the perturbation of the lipid bilayers of MCs

  • -

    Prevents the increase in intracellular calcium ion levels, which is essential for exocytosis by MCs

 [113,117,118]
NCT04479202
Palmitoylethanolamide
  • -

    Inhibits release of histamine and TNF-α by MCs

 [119]
NCT04568876, NCT04619706
Antihistamines
  • -

    Anti-inflammatory and MC-stabilizing effects have been shown for some antihistamine medicines

 [120,121,122],
NCT04370262, NCT04389567, NCT04504240, NCT04724720, NCT04565392, NCT04545008
Inhibitors of MC mediators
Zileuton
  • -

    Reduces the synthesis of leukotrienes through targeting 5-lipoxygenase enzyme
Telukast, Zafirlukast, and Montelukast
  • -

    Inhibits the binding of leukotrienes through blocking the CysLT1 receptor

  • -

    Montelukast targets SARS-Cov-2 3CL protease

 [100,123]
NCT04714515, NCT04718285
Proteases
  • -

    Prevents virus entry into cells through targeting the transmembrane protease serine 2

 [124]