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Targeting COVID-19 (SARS-CoV-2) main protease through phytochemicals of Albizia lebbeck: molecular docking, molecular dynamics simulation, MM–PBSA free energy calculations, and DFT analysis

Nalban et al., Journal of Proteins and Proteomics, doi:10.1007/s42485-024-00136-w
Apr 2024  
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Quercetin for COVID-19
24th treatment shown to reduce risk in July 2021, now with p = 0.0031 from 11 studies.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 110 treatments. c19early.org
In Silico study showing potential benefits of quercetin and other phytochemicals from Albizia lebbeck as SARS-CoV-2 main protease (Mpro) inhibitors. Using molecular docking, the authors identified four promising compounds: vicenin 2, myricetin, quercetin, and albigenic acid. 100ns molecular dynamics simulations demonstrated that these compounds significantly impacted the structure of Mpro, with quercetin showing a higher binding free energy than the positive control drug nelfinavir. Density functional theory studies revealed that vicenin 2 was the most reactive compound. The results suggest that vicenin 2, myricetin, and quercetin may be beneficial for COVID-19 by inhibiting the viral main protease.
71 preclinical studies support the efficacy of quercetin for COVID-19:
In Silico studies predict inhibition of SARS-CoV-2, or minimization of side effects, with quercetin or metabolites via binding to the spikeA,2,8,9,21,23,24,29,37,38,40,41,61-63, MproB,2,6,8,10,12,14,16,17,19,22,23,29,33,35-37,41,42,44,62-64, RNA-dependent RNA polymeraseC,2,8,31,63, PLproD,2,36,44, ACE2E,21,22,27,36,40,62, TMPRSS2F,21, nucleocapsidG,2, helicaseH,2,28,33, endoribonucleaseI,38, NSP16/10J,5, cathepsin LK,25, Wnt-3L,21, FZDM,21, LRP6N,21, ezrinO,39, ADRPP,37, NRP1Q,40, EP300R,15, PTGS2S,22, HSP90AA1T,15,22, matrix metalloproteinase 9U,30, IL-6V,20,34, IL-10W,20, VEGFAX,34, and RELAY,34 proteins. In Vitro studies demonstrate inhibition of the MproB,14,45,50,58 protein, and inhibition of spike-ACE2 interactionZ,46. In Vitro studies demonstrate efficacy in Calu-3AA,49, A549AB,20, HEK293-ACE2+AC,57, Huh-7AD,24, Caco-2AE,48, Vero E6AF,18,41,48, mTECAG,51, and RAW264.7AH,51 cells. Animal studies demonstrate efficacy in K18-hACE2 miceAI,54, db/db miceAJ,51,60, BALB/c miceAK,59, and rats65. Quercetin reduced proinflammatory cytokines and protected lung and kidney tissue against LPS-induced damage in mice59, inhibits LPS-induced cytokine storm by modulating key inflammatory and antioxidant pathways in macrophages4, and inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity53.
Nalban et al., 26 Apr 2024, peer-reviewed, 5 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperQuercetinAll
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