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pleomorphic antiviral activities. Direct viricidal ii. Radix astragali (Astragalus) - Astragalus has
activity has been demonstrated particularly against substantial Th2 inhibiting properties. As with
membrane containing viruses including coronaviruses perilla, astragalus significantly decreased
by targeting membrane components, capsid proteins, intensity of Th2 dominance-based disease
and virus replication. In addition, reversal of the processes like rhinorrhea. Mechanistic studies
340
pro-inflammatory response of epithelial cells to viral have shown that astragalus downregulates Th2
infection, and reduction of excessive mucin secretion cytokines and lowers the ratio of GATA3 (Th2
has also been observed. 330,331 cell transcription factor) to Tbet (Th1 cell
Of possible particular utility in COVID-19 is a transcription factor). 341-343 Astragalus also
species of echinacea with a long history of use in upregulates the formation of NK cells in
Western herbal medicine: Echinacea angustifolia. Also peripheral blood mononuclear cells (PBMCs)
known as narrow-leaved purple coneflower, this from SLE patients. 344
medicinal herb is native to North America. A particular
standardized extract of echinacea was shown to 4. Anti-Inflammatory Support
upregulate IL-2 and IL-8 and downregulate TNFα and Inhibition of the NLRP3 inflammasome and NFkB
IL-6 gene expression. An uncontrolled pilot study of are central to this task.
332
this preparation in 36 adults with existing respiratory a. Potassium - Maintaining blood potassium levels is
disorders (chronic bronchitis, respiratory insufficiency, important, to prevent potassium cellular efflux, which
or intrinsic asthma) found improved response to upregulates inflammasome assembly. 42
influenza vaccination and a substantial, statistically COVID-19 drug therapy guidance published on
significant increase in IgG. 333 April 8, 2020, from the American Heart Association,
Variation in extractions methods, errors in the American College of Cardiology, and the Heart
identification, and inconsistent choices in part of Rhythm Society states that hypokalemia should be
plant used present challenges in the clinical choice corrected to >4.0 mEq/L and hypomagnesemia
of echinacea products. Research on a particular corrected to >2.0 mg/dL.
345
extract cannot be reliably extrapolated to other
products. b. Curcuma longa (Tumeric) - Curcuminoids are long
used turmeric-derived compounds with well-
e. Th2 Dominance Inhibition - Understanding the documented pleotropic effects, including antiviral
complex dynamics of T cell polarization patterning and anti-inflammatory activity. 346,347
has gone far beyond Mossman’s original Th1/Th2 As has been discussed, the aggressive virulence of
dichotomy. There are currently seven known SARS-CoV-2 may be driven in part by upregulation
334
maturation fates of naïve T cells, and immunologists of NLRP3 leading to production of IL-1β, IL-18 and
no longer think of Th1 as inflammatory and Th2 as pyroptotic cell death. 348
anti-inflammatory. In patients whose baseline Curcuminoids have been shown to specifically
function likely involves Th2 dominance, indicated inhibit caspase-1 activation and IL-1β secretion through
by asthma, chronic sinusitis, allergies, or other suppressing LPS priming and NLRP3 activation. 349
known Th2-dominant disease processes, or in Regarding activity specific to SARS-CoV-2, recent
patients for whom there are other concerns about prepublication molecular docking data suggest that the
the prospect of a loss of adequate Th1 response early curcuminoids demethyoxycurcumin and curcumin
in the infection phase of illness, it may be useful to have viral replication inhibition potential against the
consider downregulating an overly exuberant Th2 main protease (Mpro) identified as likely involved in
response. viral maturation and spread. Note that a number of
i. Perilla spp. - Perilla has been shown to other flavonoids demonstrated inhibition potential in
downregulate Th2 dominance-based processes the docking study, with the strongest and best potential
like allergic airway inflammation, seasonal SARS-CoV-2 Mpro inhibitors being: kaempferol,
allergic rhinoconjunctivitis, and asthma. 335,336 quercetin, luteolin-7-glucoside, demethoxycurcumin,
Mechanistic studies suggest this effect is mediated naringenin, apigenin-7-glucoside, oleuropein,
by downregulation of Th2 effector cytokines, curcumin, catechin, and epicatechin-gallate.
350
including most importantly (IL-4), the cytokine In another molecular docking study, curcumin
driving Th2-biased autocrine responses. Perilla showed effective inhibition of SARS-Cov-2 Spike
has also been shown to inhibit platelet aggregation viral glycoprotein binding to ACE2 receptor. While
and thrombus formation. 337,338 Dietary these data are clearly preliminary, the findings suggest
supplementation with perilla seed oil in patients the potential of curcumin to halt viral entry into host
with asthma suppressed the generation of cells. Other effective flavonoids included hesperidin,
leukotriene (LT) C4. with the highest binding affinity. 351
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Yanuck—Immuno-physiological Approach to COVID-19 Integrative Medicine • Vol. 19, No. S1 • Epub Ahead of Print 23