PMC:7293470 / 1868-3408 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7293470","sourcedb":"PMC","sourceid":"7293470","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7293470","text":"In addition to current approaches such as glucocorticoids for treating advanced COVID-19 patients, there may be other drug combinations that could be helpful, some being bifunctional. As relevant examples reviewed in [5], pharmacological drugs for treatment of patients with asthma and/or chronic obstructive pulmonary disease (COPD) were developed to include both β2-agonists to relax airway smooth muscle constriction and muscarinic receptor antagonists to block M3 receptors. Another bifunctional drug was formulated to antagonize the receptors for platelet-activating factor and histamine, and mast cell secretion-blocking effects. A third anti-inflammatory drug combined an antagonist for the thromboxane receptor and cysteinyl-leukotriene antagonists into the same molecule. A bifunctional antibody construct was also developed for IL-4 and IL-13 to reduce the IL-4-dependent rise in serum IgE and IL-13-dependent airway hyperresponsiveness, lung inflammation, mucin gene expression and serum chitinase responses in mice. In this vein, bifunctional immunotherapeutic approaches could be developed for treatment of the cytokine storm in COVID-19 patients with ARDS at high risk of death. Proven and developing therapies that downregulate receptors for IL-1β, TNF-α, IL-6 and IL-2 as well as those which block macrophage migration inhibitory factor (MIF) and its homolog MIF2 through CD74 and potentially CXCR2\u00264 for MIF are all potential inhibitors of cytokine storm effects and could be combined or designed for bifunctional 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