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Clinical Recommendations and the COVID-19 main protease (M ), which is necessary
pro 7
Mechanisms of Action for viral replication. There is much excitement surrounding
pro
Background and Mechanisms of Action the recent identification of M , and it is a current
We encourage practitioners to learn about the potential pharmaceutical drug target. Kaempferol,
mechanism of invasion, replication, and pathophysiology of quercetin, luteolin-7-glucoside, demethoxycurcumin,
the SARS-CoV-2 virus. Much of what we know has been naringenin, apigenin-7-glucoside, oleuropein, curcumin,
extrapolated from basic science research on SARS-CoV-2. catechin, and epicatechin-gallate were the natural
Excellent resources are available online, including the free compounds that appeared to have the best potential to act
YouTube lectures through Dr. Roger Seheult. ii as COVID-19 Mpro inhibitors. Though further research
This document discusses the mechanisms of action of is necessary to prove their efficacy, this study provides the
a number of different botanical and nutraceutical agents. biologic plausibility and mechanistic support (COVID-19
These agents can be considered as immunoadjuvants, protease inhibition) to justify their use.
defined as substances that act to accelerate, prolong, or For these reasons, we recommend the following
enhance antigen-specific immune responses by compounds, at standard dosages, to prevent activation of
potentiating or modulating the immune response. 1 the NLRP3 inflammasome, to decrease NF-kB activation,
A coronavirus such as SARS-CoV-2 can be deadly and to potentially inhibit COVID-19 replication. There is
because of its ability to stimulate a part of the innate no literature to support a regimen of a single vs. multiple
immune response called the inflammasome, which can agents. Our recommendation is to use higher dosing and/or
cause uncontrolled release of pro-inflammatory cytokines, multiple agents when patient contextual factors
leading to cytokine storm and severe, sometimes (e.g., patient desire, pre-existing inflammation, multiple
irreversible, damage to respiratory epithelium. The co-morbidities, higher risk, etc.) and/or therapeutic
2
SARS-CoV-2 virus has been shown to activate the NLRP3 decision-making warrant such use.
inflammasome. A 2016 review article entitled “Natural
5
3,4
compounds as regulators of NLRP3 inflammasome- Download COVID-19: Nutraceutical and Botanical
mediated IL-1β production” notes that “resveratrol, Recommendations for Patients iii
curcumin, EGCG [epigallocatechin gallate], and quercetin
are potent inhibitors of NLRP3 inflammasome-mediated Recommended Interventions
IL-1β production, typically acting at more than one Quercetin
element of the involved pathways. However, it should be Quercetin has been shown to have antiviral effects
noted that these polyphenols have an even much broader against both RNA (e.g., influenza and coronavirus) and
biological effect, as they influence a variety of pathways.” DNA viruses (e.g., herpesvirus). Quercetin has a
For example, these polyphenols modulate NF-kB pleiotropic role as an antioxidant and anti-inflammatory,
upregulation, which is useful to counteract the COVID-19 modulating signaling pathways that are associated with
hyper-inflammation. 6 post-transcriptional modulators affecting post-viral
A preprint released on March 23, 2020, identified healing. 8
the ability of plant bioactive compounds to inhibit
Intervention Quercetin
Suggested dose Regular: 1 gm po bid; phytosome: 500 mg, bid
Mechanism(s) of action against Promote viral eradication or inactivation: 9,10,11,12,13
non-COVID-19 viruses • Inhibition of viral replication
Favorably modulate viral-induced pathological cellular processes:
• Modulation of NLRP3 inflammasome activation 5,14,15
Mechanistically promote resolution of collateral damage and restoration of func-
tion:
• Modulation of mast cell stabilization (anti-fibrotic)
Outcomes data supporting their Reduction of symptoms
mitigating effects on illness from
other viral strains
Strength of evidence Moderate
Risk of harm 16,17 Mimimal

ii. https://www.youtube.com/user/MEDCRAMvideos/feed
iii. https://p.widencdn.net/kvdwlh/COVID-19_Nutraceutical-and-Botanical-Recommendations-for-Patients_v4

Evans—Virus-Specific Nutraceutical and Botanical Agents Integrative Medicine • Vol. 19, No. S1 • Epub Ahead of Print 35