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All Studies   Meta Analysis    Recent:   

Potential Mechanism of Curcumin and Resveratrol against SARS-CoV-2

Wu et al., Research Square, doi:10.21203/rs.3.rs-2780614/v1
Apr 2023  
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Curcumin for COVID-19
14th treatment shown to reduce risk in February 2021
 
*, now known with p = 0.000000015 from 26 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,200+ studies for 70+ treatments. c19early.org
In Vitro study showing that curcumin and resveratrol inhibit SARS-CoV-2 infection through multiple mechanisms. Curcumin and resveratrol inhibit SARS-CoV-2 pseudovirus cell entry in HEK293-ACE2 cells with IC50 values of 18.02 μM and 8.76 μM, respectively. Combined treatment further reduces pseudovirus entry. Both compounds also inhibit activity of the SARS-CoV-2 3CL protease with IC50 values around 10-15 μM. Spike protein-induced cytokine storm is alleviated by curcumin or resveratrol through NFKB pathway inhibition in HEK293-ACE2 cells. Similarly, spike protein-mediated oxidative stress is reduced by the compounds via enhanced antioxidant system activity and ROS scavenging. Authors conclude that curcumin and resveratrol may help prevent and treat COVID-19 by inhibiting viral entry, replication, cytokine storm, and oxidative stress.
In Silico study showing potential benefits of curcumin in preventing severe COVID-19 manifestations by protecting mitochondria. Authors identified five mitochondrial dysfunction biomarkers (RECQL4, PYCR1, PIF1, POLQ, GLDC) associated with metabolic and immune dysregulation in severe COVID-19. Curcumin exhibited regulatory effects on these biomarkers and protected cells against SARS-CoV-2 spike protein-induced mitochondrial damage and oxidative stress. The study provides evidence for curcumin's ability to safeguard mitochondrial function, which may help prevent progression to severe disease.
43 preclinical studies support the efficacy of curcumin for COVID-19:
In Silico studies predict inhibition of SARS-CoV-2 with curcumin or metabolites via binding to the spikeA,17,9,20,11,4 (and specifically the receptor binding domainB,7,13,10), MproC,9,20,13,8,21,18,23,6,15,12,33,10,4, RNA-dependent RNA polymeraseD,19,10, ACE2E,11,12,14, nucleocapsidF,5,22, and nsp10G,22 proteins. In Vitro studies demonstrate inhibition of the spikeA,28 (and specifically the receptor binding domainB,36), MproC,33,35,28,16, ACE2E,36, and TMPRSS2H,36 proteins. In Vitro studies demonstrate efficacy in Calu-3I,34, A549J,28, 293TK,1, HEK293-hACE2L,26,16, 293T/hACE2/TMPRSS2M,27, Vero E6N,34,10,20,30,28,26,6,29,32, and SH-SY5YO,25 cells. Curcumin is predicted to inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain and the human ACE2 receptor for the delta and omicron variants7, decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells32, and alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress1.
Wu et al., 13 Apr 2023, preprint, 6 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
Potential Mechanism of Curcumin and Resveratrol against SARS-CoV-2
Wei Wu, Junxi Wu, Xuxu Ji, Ji Liu, Fuchang Geng
doi:10.21203/rs.3.rs-2780614/v1
Recently, World Health Organization predicted a near end of COVID-19 pandemic. However, the prediction should be interpreted cautiously. Due to SARS-CoV-2 continuous mutation-evolve, limited durability of infection-acquired protection in individuals with hybrid immunity, and the effects of long COVID-19 or Post-COVID-19 syndrome, COVID-19 may continue to be a worldwide threat. Alternative therapeutics are incorporated into some countries' health guidelines for COVID-19. Qiannan herbal, an ancient medical book of Yi Nationality in China, recorded that grapes and turmeric were often used to treat respiratory diseases. Curcumin and resveratrol are the primary bioactive compounds in turmeric and grapes, respectively. The clinical trials con rmed that curcumin or resveratrol supplementation could cause moderate or marked improvements in COVID-19 patients. Exploring the potential mechanisms is of great signi cance. This study found that curcumin and resveratrol could effectively inhibit SARS-CoV-23CLpro activity and spike protein-mediated cell entry. Curcumin and resveratrol could signi cantly alleviate spike protein-mediated cytokine storm via inhibiting over-activation of NFKB, and effectively ameliorate spike protein-mediated oxidative stress through scavenging ROS and enhancing function of antioxidation system. The combined treatment showed a better effect than alone treatment. Therefore, curcumin and resveratrol could inhibit SARS-CoV-23C-like proteinase activity and Spike protein-mediated cell entry, cytokine storm, and oxidative stress.
In conclusion, curcumin and resveratrol could inhibit SARS-CoV-2 3CLpro activity and spike proteinmediated cell entry, cytokine storm, and oxidative stress. The above conclusions are shown in Supplementary Fig. 5 . Our study provides a reference of nutrient supplementation for preventing and treating COVID-19. Methods Venn analysis and Enrichment analysis Firstly, COVID-19, curcumin, and resveratrol were separately input into Gene or Pubchem database at National Center for Biotechnology Information (NCBI) and ltered with Homo sapiens, and the gene sets were Cell culture and reagents Vero cells and HEK293T-hACE2 cells were obtained from the Laboratory of Biochemistry and Molecular Biology, Sichuan University. Cells were maintained in Dulbecco's Modi ed Eagle's Medium (DMEM) supplemented with 10% FBS and incubated at 37°C with 5% CO2. Fetal bovine serum (FBS), DMEM, and phosphate-buffered saline (PBS) were bought from Gibco (Grand Island, NY, USA). Pyrrolidinedithiocarbamate ammonium (PDTC), curcumin, and resveratrol were obtained from Solarbio. Ebselen was purchased from Beyotime. Cell viability assay Vero E6 cells were..
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