Myricetin Inhibits SARS-CoV-2 Viral Replication by Targeting Mpro and Ameliorates Pulmonary Inflammation

Tu, Xiao; Cui, Mengqi; Zheng, Caijuan; Wang, Ming; Sun, Ronghao; Gao, Dandi; Bao, Jiali; Ren, Shanfa; Yang, Bo; Lin, Jianping; Li, Xiaoping; Li, Dongmei; Yang, Cheng; Zhou, Honggang

doi:10.3389/fphar.2021.669642

Cited by 66 publications

(65 citation statements)

References 42 publications

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“…Similarly, varying cross-study data of quercetagenin, with cell-free and cell-based assays, report drastically different active concentration markers [118,119]. In general, the efficacy of myricetin is higher than quercetin, with cell-free methods reporting generally weaker inhibitory capacities against 3CLpro than cell-based assays (Table 1) [117][118][119]122]. Moreover, myricetin is a promising compound given its inhibitory effect against viruses and weak cellular cytotoxicity [117].…”

Section: Flavonols and Flavanonolsmentioning

confidence: 99%

“…Among these, 3CLpro was investigated against flavonols and flavones more than other subclasses of flavonoids. Tables 1 and 2 summarize the in vitro activities of various flavonoids against SARS-CoV-2 3CLpro, and PLpro reported in the literature, respectively [117][118][119][120][121][122][123][124][125][126][127][128].…”

Section: Antiviral Activity Of Flavonoids Against Sars-cov-2 Proteases (3clpro and Plpro)mentioning

confidence: 99%

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Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

Kaul

Paul

Kumar

et al. 2021

IJMS

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The ongoing COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a globally leading public health concern over the past two years. Despite the development and administration of multiple vaccines, the mutation of newer strains and challenges to universal immunity has shifted the focus to the lack of efficacious drugs for therapeutic intervention for the disease. As with SARS-CoV, MERS-CoV, and other non-respiratory viruses, flavonoids present themselves as a promising therapeutic intervention given their success in silico, in vitro, in vivo, and more recently, in clinical studies. This review focuses on data from in vitro studies analyzing the effects of flavonoids on various key SARS-CoV-2 targets and presents an analysis of the structure-activity relationships for the same. From 27 primary papers, over 69 flavonoids were investigated for their activities against various SARS-CoV-2 targets, ranging from the promising 3C-like protease (3CLpro) to the less explored nucleocapsid (N) protein; the most promising were quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid. We further review promising in silico studies featuring activities of flavonoids against SARS-CoV-2 and list ongoing clinical studies involving the therapeutic potential of flavonoid-rich extracts in combination with synthetic drugs or other polyphenols and suggest prospects for the future of flavonoids against SARS-CoV-2.

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Section: Flavonols and Flavanonolsmentioning

confidence: 99%

Section: Antiviral Activity Of Flavonoids Against Sars-cov-2 Proteases (3clpro and Plpro)mentioning

confidence: 99%

Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

Kaul

Paul

Kumar

et al. 2021

IJMS

View full text Add to dashboard Cite

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“…Among the molecules investigated, natural compounds have a prominent role [ 6 ] due to their large diffusion, high variety of molecular features, and wide spectrum of effects in cells. Molecules with confirmed in vitro inhibitory activity against 3CLpro include baicalein [ 7 , 8 ], quercetin [ 9 ], rutin [ 10 ], epigallocatechin-3-gallate [ 11 ], and myricetin [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Sub-Micromolar Inhibition of SARS-CoV-2 3CLpro by Natural Compounds

et al. 2021

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Inhibiting the main protease 3CLpro is the most common strategy in the search for antiviral drugs to fight the infection from SARS-CoV-2. We report that the natural compound eugenol is able to hamper in vitro the enzymatic activity of 3CLpro, the SARS-CoV-2 main protease, with an inhibition constant in the sub-micromolar range (Ki = 0.81 μM). Two phenylpropene analogs were also tested: the same effect was observed for estragole with a lower potency (Ki = 4.1 μM), whereas anethole was less active. The binding efficiency index of these compounds is remarkably favorable due also to their small molecular mass (MW < 165 Da). We envision that nanomolar inhibition of 3CLpro is widely accessible within the chemical space of simple natural compounds.

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“…In silico studies show that myricetin can bind to SARS-CoV-2 Mpro with the chromone ring of the compound by interacting with His41 (one of the catalytic dyad amino acid residues of Mpro) through π-π stacking, as well as the formation of hydrogen bonds between 3 -, 4 -and 7-hydroxyl of myricetin and Phe140, Glu166, and Asp187 of Mpro [79]. Myricetin also showed an anti-inflammatory effect on bleomycin-induced pulmonary inflammation; infiltration of inflammatory cells and secretion of inflammatory cytokines like interleukin-6 (IL-6), IL-1α, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were inhibited [79]. Two flavonoids, dihydroxy-6 -methoxy-3 ,5 -dimethylchalcone and myricetin-3 ,5 -dimethyl ether 3-O-β-D-galactopyranoside isolated from Cleistocalyx operculatus (Roxb.)…”

Section: Flavonoids-classification Structure and Anti-viral Activitiesmentioning

confidence: 99%

Nanotechnology Applications of Flavonoids for Viral Diseases

et al. 2021

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Recent years have witnessed the emergence of several viral diseases, including various zoonotic diseases such as the current pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Other viruses, which possess pandemic-causing potential include avian flu, Ebola, dengue, Zika, and Nipah virus, as well as the re-emergence of SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) coronaviruses. Notably, effective drugs or vaccines against these viruses are still to be discovered. All the newly approved vaccines against the SARS-CoV-2-induced disease COVID-19 possess real-time possibility of becoming obsolete because of the development of ‘variants of concern’. Flavonoids are being increasingly recognized as prophylactic and therapeutic agents against emerging and old viral diseases. Around 10,000 natural flavonoid compounds have been identified, being phytochemicals, all plant-based. Flavonoids have been reported to have lesser side effects than conventional anti-viral agents and are effective against more viral diseases than currently used anti-virals. Despite their abundance in plants, which are a part of human diet, flavonoids have the problem of low bioavailability. Various attempts are in progress to increase the bioavailability of flavonoids, one of the promising fields being nanotechnology. This review is a narrative of some anti-viral dietary flavonoids, their bioavailability, and various means with an emphasis on the nanotechnology system(s) being experimented with to deliver anti-viral flavonoids, whose systems show potential in the efficient delivery of flavonoids, resulting in increased bioavailability.

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Myricetin Inhibits SARS-CoV-2 Viral Replication by Targeting Mpro and Ameliorates Pulmonary Inflammation

Cited by 66 publications

References 42 publications

Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

Sub-Micromolar Inhibition of SARS-CoV-2 3CLpro by Natural Compounds

Nanotechnology Applications of Flavonoids for Viral Diseases

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