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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