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Treatment with Quercetin inhibits SARS-CoV-2 N protein-induced acute kidney injury by blocking Smad3-dependent G1 cell cycle arrest

Wu et al., Molecular Therapy, doi:10.1016/j.ymthe.2022.12.002
Dec 2022  
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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 109 treatments. c19early.org
Mouse study showing quercetin can significantly inhibit SARS-CoV-2 induced acute kidney injury via blocking of SARS-CoV-2 N-Smad3-mediated cell death.
Bioavailability. Quercetin has low bioavailability and studies typically use advanced formulations to improve bioavailability which may be required to reach therapeutic concentrations.
68 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,6,7,19,21,22,27,35,36,38,39,59,60, MproB,4,6,8,10,12,14,15,17,20,21,27,31,33-35,39,40,42,60,61, RNA-dependent RNA polymeraseC,6,29, PLproD,34,42, ACE2E,19,20,25,34,38,60, TMPRSS2F,19, helicaseG,26,31, endoribonucleaseH,36, NSP16/10I,3, cathepsin LJ,23, Wnt-3K,19, FZDL,19, LRP6M,19, ezrinN,37, ADRPO,35, NRP1P,38, EP300Q,13, PTGS2R,20, HSP90AA1S,13,20, matrix metalloproteinase 9T,28, IL-6U,18,32, IL-10V,18, VEGFAW,32, and RELAX,32 proteins. In Vitro studies demonstrate inhibition of the MproB,12,43,48,56 protein, and inhibition of spike-ACE2 interactionY,44. In Vitro studies demonstrate efficacy in Calu-3Z,47, A549AA,18, HEK293-ACE2+AB,55, Huh-7AC,22, Caco-2AD,46, Vero E6AE,16,39,46, mTECAF,49, and RAW264.7AG,49 cells. Animal studies demonstrate efficacy in K18-hACE2 miceAH,52, db/db miceAI,49,58, BALB/c miceAJ,57, and rats62. Quercetin reduced proinflammatory cytokines and protected lung and kidney tissue against LPS-induced damage in mice57, inhibits LPS-induced cytokine storm by modulating key inflammatory and antioxidant pathways in macrophages2, and inhibits SARS-CoV-2 ORF3a ion channel activity, which contributes to viral pathogenicity and cytotoxicity51.
Wu et al., 12 Dec 2022, China, peer-reviewed, 9 authors. Contact: hylan@cuhk.edu.hk, yuxueqing@gdph.org.cn, wangxiao773@hotmail.com.
This PaperQuercetinAll
Treatment with quercetin inhibits SARS-CoV-2 N protein-induced acute kidney injury by blocking Smad3-dependent G1 cell-cycle arrest
Wenjing Wu, Wenbiao Wang, Liying Liang, Junzhe Chen, Biao Wei, Xiao-Ru Huang, Professor Xiaoqin Wang, Xueqing Yu, Professor Hui-Yao Lan
Molecular Therapy, doi:10.1016/j.ymthe.2022.12.002
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Author contributions W.W. and W.B. performed the experiment, analyzed the data, and wrote the manuscript; L.L., J.C., B.W. and X.R.H. prepared the animal model and analyzed data; X.W. and X.Y. supervised experiments; H.Y.L. designed, supervised the experiments, and revised the manuscript. Declaration of interests All the authors declared no competing interests.
References
Andrade, Rodrigues, Gomes, Noronha, Acute Kidney Injury as a Condition of Renal Senescence, Cell Transplant
Bulow Anderberg, Luther, Berglund, Larsson, Rubertsson et al., n a l P r e -p r o o f
Caceres, Savickas, Murray, Umanath, Uduman et al., High SARS-CoV-2 Viral Load in Urine Sediment Correlates with Acute Kidney Injury and Poor COVID-19 Outcome, J Am Soc Nephrol
Carlson, Hsu, Conboy, Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells, Nature
Chan, Chaudhary, Saha, Chauhan, Vaid et al., AKI in Hospitalized Patients with COVID-19, J Am Soc Nephrol
Chen, A potential treatment of COVID-19 with TGF-β blockade, Int J Biol Sci
Chen, Guan, Qiu, Xu, Bai et al., SARS-CoV-2 nucleocapsid protein triggers hyperinflammation via protein-protein interaction-mediated intracellular Cl(-) accumulation in respiratory epithelium, Signal Transduct Target Ther
Chen, Wang, Tang, Huang, Yu et al., Inflammatory stress in SARS-COV-2 associated Acute Kidney Injury, Int J Biol Sci
Chen, Wu, Wang, Tang, Lan, Role of TGF-β Signaling in Coronavirus Disease 2019, Integr Med Nephrol Androl
Cheng, Luo, Wang, Zhang, Wang et al., Kidney disease is associated with in-hospital death of patients with COVID-19, Kidney Int
Derosa, Maffioli, D'angelo, Di Pierro, A role for quercetin in coronavirus disease 2019 (COVID-19), Phytother Res
Di Pierro, Derosa, Maffioli, Bertuccioli, Togni et al., Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 Infection: A Prospective, Randomized, Controlled, and Open-Label Study, Int J Gen Med
Di Pierro, Iqtadar, Khan, Ullah Mumtaz, Masud Chaudhry et al., Potential Clinical Benefits of Quercetin in the Early Stage of COVID-19: Results of a Second, Pilot, Randomized, Controlled and Open-Label Clinical Trial, Int J Gen Med
Diao, Wang, Wang, Feng, Zhang et al., Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection, Nat Commun
Ferreira-Gomes, Kruglov, Durek, Heinrich, Tizian et al., SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself, Nat Commun
Fu, Tang, Huang, Feng, Xu et al., Smad7 protects against acute kidney injury by rescuing tubular epithelial cells from the G1 cell cycle arrest, Clin Sci (Lond)
Gao, Gao, Liu, Nie, Sun et al., Identification and functional analysis of the SARS-COV-2 nucleocapsid protein, BMC Microbiol
Gao, He, Liang, Liu, Liu et al., Quercetin ameliorates podocyte injury via inhibition of oxidative stress and the TGF-β1/Smad pathway in DN rats, RSC Adv
Ghazavi, Ganji, Keshavarzian, Rabiemajd, Mosayebi, Cytokine profile and disease severity in patients with COVID-19, Cytokine
Gradin, Andersson, Luther, Anderberg, Rubertsson et al., Urinary cytokines correlate with acute kidney injury in critically ill COVID-19 patients, Cytokine
Gu, Peng, Lin, Qin, Liang et al., P16(INK4a) played a critical role in exacerbating acute tubular necrosis in acute kidney injury, Am J Transl Res
Gu, Zhang, Cen, Wu, Lu et al., Quercetin as a potential treatment for COVID-19-induced acute kidney injury: Based on network pharmacology and molecular docking study, PLoS One
Gupta, Coca, Chan, Melamed, Brenner et al., AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19, J Am Soc Nephrol
Hamidi, Kadamboor, Veethil, Hamidi, Role of pirfenidone in TGF-β pathways and other inflammatory pathways in acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection: a theoretical perspective, Pharmacol Rep
He, Wei, Liu, Yi, Liu et al., AKI on CKD: heightened injury, suppressed repair, and the underlying mechanisms, Kidney Int
Huang, Bai, He, Xie, Zhou, Review on the potential action mechanisms of Chinese medicines in treating Coronavirus Disease 2019 (COVID-19), Pharmacol Res
Huntington, Carlsen, So, Piesche, Liang et al., Integrin/TGF-β1 Inhibitor GLPG-0187 Blocks SARS-CoV-2 Delta and Omicron Pseudovirus Infection of Airway Epithelial Cells In Vitro
J O U R, n a l P r e -p r o o f Smad3-dependent cell cycle arrest at the G1 phase. (A) Co-IP detects that quercetin dosedependently inhibits the interaction between Flag-N and HA-Smad3 in HEK293T cells coexpressing Flag-SARS-CoV-2 N and HA-Smad3; (B) Western blotting detects that like a Smad3 inhibitor SIS3, pre-treatment with quercetin (64μM) for 24hr is able to inhibit SARS-CoV-2 N protein induced Smad3 signaling in HK-2 cells under high AGE(50µg/ml, 30 mins) conditions ; (C) Western blotting reveals that like a Smad3 inhibitor SIS3, pre-treatment with quercetin (64μM) for 24hr is able to inhibit SARS-CoV-2 N protein induced p-Smad3 nuclear translocation in HK-2 cells under high AGE(50µg/ml, 2hr) conditions; (D-E) Western blotting and real-time PCR demonstrate that like a Smad3 inhibitor SIS3, pre-treatment with quercetin (64μM) for 24hr is able to inhibit SARS-CoV-2 N protein induced upregulation of p16 and cyclin D1 downregulation in HK-2 cells under high AGE (50µg/ml) conditions; (F) Flowcytometry analysis reveals that pretreated with quercetin (64μM) for 24hr is able to inhibit SARS-CoV-2 N protein induced cell cycle arrest at the G1 phase while increasing the cell progression into the S-phase in HK-2 cells under high AGE (50µg/ml) conditions. Data are presented as mean ± SEM for at least three independent experiments
Jansen, Reimer, Nagai, Varghese, Overheul et al., SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids, Cell Stem Cell
Kang, Jin, Jiang, Zhang, Zhang et al., Efficacy and mechanisms of traditional Chinese medicine for COVID-19: a systematic review, Chin Med
Khan, Zeb, Ahsan, Ahmed, Ali et al., SARS-CoV-2 nucleocapsid and Nsp3 binding: an in silico study, Arch Microbiol
Lai, Tang, Huang, Tang, Xu et al., C-reactive protein promotes acute kidney injury via Smad3-dependent inhibition of CDK2/cyclin E, Kidney Int
Lan, Mu, Nikolic-Paterson, Atkins, A novel, simple, reliable, and sensitive method for multiple immunoenzyme staining: use of microwave oven heating to block antibody crossreactivity and retrieve antigens, J Histochem Cytochem
Larsson, Frithiof, Hultstrom, Increased levels of plasma cytokines and correlations to organ failure and 30-day mortality in critically ill Covid-19 patients, Cytokine
Lee, Wolstein, Pudasaini, Plotkin, INK4a deletion results in improved kidney regeneration and decreased capillary rarefaction after ischemiareperfusion injury, Am J Physiol Renal Physiol
Legrand, Bell, Forni, Joannidis, Koyner et al., Pathophysiology of COVID-19-associated acute kidney injury, Nat Rev Nephrol
Li, Deng, Guo, Yan, Lu et al., Effective dose/duration of natural flavonoid quercetin for treatment of diabetic nephropathy: A systematic review and meta-analysis of rodent data, Phytomedicine
Lu, Wu, Liu, Ruan, Zhang et al., Quercetin ameliorates kidney injury and fibrosis by modulating M1/M2 macrophage polarization, Biochem Pharmacol
Luo, Bao, Weng, Bai, Feng et al., The protective effect of quercetin on macrophage pyroptosis via TLR2/Myd88/NF-κB and ROS/AMPK pathway, Life Sci
Lyu, Fan, Xiao, Wang, Xu et al., Traditional Chinese medicine in COVID-19, Acta Pharm Sin B
Mangalmurti, Hunter, Cytokine Storms: Understanding COVID-19, Immunity
Menez, Moledina, Thiessen-Philbrook, Wilson, Obeid et al., Prognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19, Am J Kidney Dis
Munafo, Donati, Brindani, Ottonello, Armirotti et al., Quercetin and luteolin are single-digit micromolar inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase, Sci Rep
Nadim, Forni, Mehta, Connor, Jr et al., COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup, Nat Rev Nephrol
Ouyang, Gong, Zhu, Gong, Association of acute kidney injury with the severity and mortality of SARS-CoV-2 infection: A meta-analysis, Am J Emerg Med
Pan, Fang, Zhang, Pan, Liu et al., Chinese herbal compounds against SARS-CoV-2: Puerarin and quercetin impair the binding of viral S-protein to ACE2 receptor, Comput Struct Biotechnol J
Pan, Shen, Yu, Ge, Chen et al., SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation, Nat Commun
Price, Safirstein, Megyesi, The cell cycle and acute kidney injury, Kidney Int
Puelles, Lutgehetmann, Lindenmeyer, Sperhake, Wong et al., Multiorgan and Renal Tropism of SARS-CoV-2, N Engl J Med
Saakre, Mathew, Ravisankar, Perspectives on plant flavonoid quercetin-based drugs for novel SARS-CoV-2, Beni Suef Univ J Basic Appl Sci
Saeedi-Boroujeni, Mahmoudian-Sani, Anti-inflammatory potential of Quercetin in COVID-19 treatment, J Inflamm (Lond)
Su, Yang, Wan, Yi, Tang et al., Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China, Kidney Int
Tan, Wang, Deng, Zhong, Yan et al., Quercetin protects against cisplatin-induced acute kidney injury by inhibiting Mincle/Syk/NF-κB signaling maintained macrophage inflammation, Phytother Res
Tang, Li, Zhang, Li, Li et al., Quercetin liposomes ameliorate streptozotocin-induced diabetic nephropathy in diabetic rats, Sci Rep
Ueda, Tominaga, Ochi, Sakurai, Nishimura et al., TGF-β1 is involved in senescence-related pathways in glomerular endothelial cells via p16 translocation and p21 induction, Sci Rep
V'kovski, Kratzel, Steiner, Stalder, Thiel, Coronavirus biology and replication: implications for SARS-CoV-2, Nat Rev Microbiol
Vogel, Mustroph, Staudner, Leininger, Hubauer et al., Kidney injury molecule-1: potential biomarker of acute kidney injury and disease severity in patients with COVID-19, J Nephrol
Wang, Chen, Hu, Pan, Liang et al., SARS-CoV-2 N Protein Induces Acute Kidney Injury via Smad3-Dependent G1 Cell Cycle Arrest Mechanism, Adv Sci (Weinh)
Wang, Chen, Yu, Lan, Signaling mechanisms of SARS-CoV-2 Nucleocapsid protein in viral infection, cell death and inflammation, Int J Biol
Witkowski, Tizian, Ferreira-Gomes, Niemeyer, Jones et al., Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells, Nature
Wu, Ma, Cai, Zhuang, Zhao et al., RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid protein facilitates NF-κB hyper-activation and inflammation, Signal Transduct Target Ther
Wu, Zhao, Yu, Chen, Wang et al., A new coronavirus associated with human respiratory disease in China, Nature
Yang, Islam, Wang, Li, Chen, Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective, Int J Biol Sci
Yang, Rao, Structural biology of SARS-CoV-2 and implications for therapeutic development, Nat Rev Microbiol
Yang, Xie, Tu, Fu, Xu et al., The signal pathways and treatment of cytokine storm in COVID-19, Signal Transduct Target Ther
Zhao, Nicholls, Chen, Severe acute respiratory syndromeassociated coronavirus nucleocapsid protein interacts with Smad3 and modulates transforming growth factor-β signaling, J Biol Chem
Zheng, Sun, Yu, Shi, Zhu et al., Interactome Analysis of the Nucleocapsid Protein of SARS-CoV-2 Virus, Pathogens
Zheng, Zhao, Yang, Acute Kidney Injury in COVID-19: The Chinese Experience, Semin Nephrol
Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet
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