Natural compound myricetin shows antiviral potential against SARS-CoV-2

Natural compounds have become a popular source of interest for drug development due to some successes in their employment against cancer, HIV, malaria, and heart disease. Some natural compounds — flavonoids, garlic, naturally occurring coumarin, and green tea polyphenols — have had higher affinities than some marketed drugs.

New findings from a team of Chinese researchers suggest natural compounds — specifically the flavonoid myricetin — could also be a potential drug candidate for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Myricetin not only inhibited SARS-CoV-2 main protease (Mpro) but it also demonstrated anti-inflammatory effects in vivo.

The research team writes:

Oleuropein, myricetin and vitexin have high affinity with Mpro. However, only myricetin exhibit significant inhibition with IC50 3.684 ± 0.076 μM by FRET-based assay. Structurally, myricetin can interact with His41 through π-π stacking and form hydrogen bonds with Phe140, Glu166 and Asp187 in the catalytic center of SARS-CoV-2 Mpro.”

The study “Myricetin Inhibits SARS-CoV-2 Viral Replication by Targeting Mpro and Ameliorates Pulmonary Inflammation” is published in the journal Frontiers in Pharmacology.

Myricetin exhibited high inhibitory activity against SARS-CoV-2

The researchers evaluated the binding affinity of 15 natural compounds consisting of flavonoids, coumarins, terpenoids, phenolic, aldehyde, and steroid compounds to SARS-CoV-2 Mpro. They also studied 17 chemical compounds via molecular docking to the SARS-CoV-2 Mpro crystal structure. Of the 32 candidates, only 4 were capable of inhibiting docking, indicating effective inhibition of SARS-CoV-2 Mpro activity.

A fluorescence resonance energy transfer enzymatic assay was used to screen the potential candidates. They narrowed down their choices to the flavonoid myricetin because it inhibited enzymatic activity up to 97.79%.

“Given the encouraging results from the primary screening, we then further characterized the inhibitory activity of myricetin in a dose gradient and the myricetin inhibited SARS-CoV-2 Mpro with 50% inhibitory concentration values (IC50) of 3.684 ± 0.076 μM,” wrote the researchers.

Myricetin reduces lung inflammation

Preclinical results suggest myricetin may be helpful against SARS-CoV-2 damage in the body.

The researchers treated mice with the chemotherapy drug bleomycin for 7 days to create a lung injury. When myricetin was administered, the team found that myricetin significantly ameliorated the infiltration of inflammatory cells in mice.

In the bronchoalveolar lavage fluid in the lungs, there was an upregulation in the total number of inflammatory cells and the number of different inflammatory cells. But in a dose-dependent manner, mice treated with myricetin showed a down-regulation of inflammatory cells.

Additionally, myricetin significantly inhibited the expression levels of inflammatory factors such as IL-6, TNF-α, IFN-γ and IL-1α in the bronchoalveolar lavage fluid.

Overall, the results suggest that myricetin could be a potent inhibitor as a first-line defense for COVID-19. There is also potential for use as an anti-inflammatory drug. More clinical research, to establish the safety and efficacy of myricetin, will be needed to build on these promising findings.

Journal reference:
Jocelyn Solis-Moreira

Written by

Jocelyn Solis-Moreira

Jocelyn Solis-Moreira graduated with a Bachelor's in Integrative Neuroscience, where she then pursued graduate research looking at the long-term effects of adolescent binge drinking on the brain's neurochemistry in adulthood.


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