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COMMERCIALLY AVAILABLE FLAVONOLS ARE BETTER SARS-COV-2 INHIBITORS THAN ISOFLAVONE AND FLAVONES
COVID-19
Produtos naturais
Flavonóides
Ancoragem molecular
Células Calu-3
Exonuclease
Protease
COVID-19
Natural products
Flavonoids
Molecular docking
Calu-3 cells
Exonuclease
Protease
Author
Affilliation
Abstract
Despite the fast development of vaccines, severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) is still circulating and generating variants of concern (VoC) that escape the humoral
immune response. In this context, the search for anti-SARS-CoV-2 compounds is still essential. A class
of natural polyphenols known as flavonoids, frequently available in fruits and vegetables, is widely
explored in the treatment of different diseases and used as a scaffold for the design of novel drugs.
Therefore, herein we evaluate seven flavonoids divided into three subclasses, isoflavone (genistein),
flavone (apigenin and luteolin) and flavonol (fisetin, kaempferol, myricetin, and quercetin), for
COVID-19 treatment using cell-based assays and in silico calculations validated with experimental
enzymatic data. The flavonols were better SARS-CoV-2 inhibitors than isoflavone and flavones. The
increasing number of hydroxyl groups in ring B of the flavonols kaempferol, quercetin, and myricetin
decreased the 50% effective concentration (EC50) value due to their impact on the orientation of
the compounds inside the target. Myricetin and fisetin appear to be preferred candidates; they are
both anti-inflammatory (decreasing TNF- levels) and inhibit SARS-CoV-2 mainly by targeting the
processability of the main protease (Mpro) in a non-competitive manner, with a potency comparable
to the repurposed drug atazanavir. However, fisetin and myricetin might also be considered hits that
are amenable to synthetic modification to improve their anti-SARS-CoV-2 profile by inhibiting not
only Mpro, but also the 30–50 exonuclease (ExoN).
Keywords in Portuguese
SARS-CoV-2COVID-19
Produtos naturais
Flavonóides
Ancoragem molecular
Células Calu-3
Exonuclease
Protease
Keywords
SARS-CoV-2COVID-19
Natural products
Flavonoids
Molecular docking
Calu-3 cells
Exonuclease
Protease
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