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All Studies   Meta Analysis   Recent:  

Vitamin C promotes ACE2 degradation and protects against SARS‐CoV‐2 infection

Zuo et al., EMBO reports, doi:10.15252/embr.202256374 (date from preprint)
Jul 2022  
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In Vitro and mouse study showing that vitamin C inhibits SARS-CoV-2. Vitamin C lowered ACE2 protein levels in a dose-dependent manner at a concentration of 1-10mM in both cell and humanized ACE2 mouse models.
9 preclinical studies support the efficacy of vitamin C for COVID-19:
Vitamin C plays a key role in the immune system, supporting the production and function of leukocytes, or white blood cells, which defend against infection and disease, including the production of lymphocytes, which make antibodies, and enhancing phagocytosis, the process by which immune system cells ingest and destroy viruses and infected cells. Vitamin C is an antioxidant, protecting cells from damage caused by free radicals. Preclinical research shows that vitamin C inhibits SARS-CoV-2 3CLpro Malla, Đukić, reduces ACE2 levels in a dose-dependent manner, and inhibits SARS-CoV-2 infection Zuo. Intracellular levels of vitamin C decline during COVID-19 hospitalization Boerenkamp, suggesting ongoing utilization and depletion of vitamin C. Threonic acid, a metabolite of vitamin C, is lower in mild and severe cases Albóniga, consistent with increased need for and metabolization of vitamin C with moderate infection, but more limited ability to produce threonic acid in severe infection due to depletion or existing lower levels of vitamin C. Symptomatic COVID-19 is associated with a lower frequency of natural killer (NK) cells Graydon, and vitamin C has been shown to improve NK cell numbers and functioning Vojdani.
Zuo et al., 15 Jul 2022, China, peer-reviewed, 15 authors.
Contact: huizheng@suda.edu.cn (corresponding author).
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Abstract: bioRxiv preprint doi: https://doi.org/10.1101/2022.07.14.499651; this version posted July 15, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Vitamin C is an efficient natural product for prevention of 2 SARS-CoV-2 infection by targeting ACE2 in both cell and in 3 vivo mouse models 4 5 Yibo Zuo,1,2 Zhijin Zheng,1,2 Yingkang Huang,5 Jiuyi He,1,2 Lichao Zang,4 6 Tengfei Ren,1,2 Xinhua Cao,1,2 Ying Miao,1,2 Yukang Yuan,1,2 Yanli Liu,3 Feng 7 Ma,5 Sheng Tian,3 Jianfeng Dai,1,2 Qiang Ding,6 Hui Zheng1,2,7,* 8 9 1 International Institute of Infection and Immunity, Institutes of Biology and Medical 10 Sciences, Suzhou 11 2 Jiangsu Key Laboratory of Infection and Immunity, Suzhou 12 3 College of Pharmaceutical Sciences, Suzhou 13 4 The Third Affiliated Hospital of Soochow University, Changzhou 14 Soochow University, Jiangsu 215123, China 15 5 16 of Medical Sciences and Peking Union Medical College, Beijing 10005; Suzhou 17 Institute of Systems Medicine, Jiangsu 215123, China 18 6 19 Innovation Center for Structural Biology, Tsinghua University, Beijing 10084, China 20 7 21 *Correspondence: huizheng@suda.edu.cn CAMS Key Laboratory of Synthetic Biology Regulatory Elements, Chinese Academy Center for Infectious Disease Research, School of Medicine, Beijing Advanced Lead contact 22 23 24 1 bioRxiv preprint doi: https://doi.org/10.1101/2022.07.14.499651; this version posted July 15, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 25 SUMMARY 26 ACE2 is a major receptor for cell entry of SARS-CoV-2. Despite advances in 27 targeting ACE2 to inhibit SARS-CoV-2's binding, how to efficiently and flexibly 28 control ACE2 levels for prevention of SARS-CoV-2 infection has not been 29 explored. Here, we revealed Vitamin C (VitC) administration as an effective 30 strategy to prevent SARS-CoV-2 infection. VitC reduced ACE2 protein levels in 31 a dose-dependent manner, while partial reduction of ACE2 can greatly restrict 32 SARS-CoV-2 infection. Further studies uncovered that USP50 is a crucial 33 regulator of ACE2 protein levels, and VitC blocks the USP50-ACE2 interaction, 34 thus promoting K48-linked polyubiquitination at Lys788 and degradation of 35 ACE2, without disrupting ACE2 transcriptional expression. Importantly, VitC 36 administration reduced host ACE2 and largely blocked SARS-CoV-2 infection 37 in mice. This study identified an in vivo ACE2 balance controlled by both 38 USP50 and an essential nutrient VitC, and revealed a critical role and 39 application of VitC in daily protection from SARS-CoV-2 infection. 40 41 Highlights 42 VitC reduces ACE2 protein levels in a dose-dependent manner 43 VitC and USP50 regulate K48-linked ubiquitination at Lys788 of ACE2 44 VitC blocks the interaction between USP50 and ACE2 45 VitC administration lowers host ACE2 and prevents SARS-CoV-2 infection 46 in vivo 47 48 2 bioRxiv preprint doi: https://doi.org/10.1101/2022.07.14.499651; this version posted July 15, 2022. The copyright holder for this preprint (which was not certified by..
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