Commercially Available Flavonols Are Better SARS-CoV-2 Inhibitors than Isoflavone and Flavones
Year: 2022
Type: article
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-α 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 3′–5′ exonuclease (ExoN).
Source: Viruses
DOI: 10.3390/v14071458
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,513
Funders: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Fundação Oswaldo Cruz, Foundation for Scientific and Technological Development in Health, National Institutes of Health, National Institute of Allergy and Infectious Diseases
Awards: G1383679146, G1419661400, G1497928764, G1677423749, G1729847405, G1840770272, G2311368543, G2362805151, G2823776494, G304889910, G3053499983, G3325778992, G4276207862, G4311951901, G4525194000, G47252533, G4791414616, G4794594734, Metropolitan AntiViral Drug Accelerator, G5338584205, G608118834, G6706793559, G6928025755, G6997875432, G7233804116, G7321767412, G760711862, G7697315321, G7940528614, G8637371721, G8738012545, G8777331534
OpenAlex ID: W4283739379