Vitamin C promotes ACE2 degradation and protects against SARS‐CoV‐2 infection
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
3CL
pro 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).
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was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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.
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Vitamin C is an efficient natural product for prevention of
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SARS-CoV-2 infection by targeting ACE2 in both cell and in
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vivo mouse models
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Yibo Zuo,1,2 Zhijin Zheng,1,2 Yingkang Huang,5 Jiuyi He,1,2 Lichao Zang,4
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Tengfei Ren,1,2 Xinhua Cao,1,2 Ying Miao,1,2 Yukang Yuan,1,2 Yanli Liu,3 Feng
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Ma,5 Sheng Tian,3 Jianfeng Dai,1,2 Qiang Ding,6 Hui Zheng1,2,7,*
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1
International Institute of Infection and Immunity, Institutes of Biology and Medical
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Sciences, Suzhou
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2
Jiangsu Key Laboratory of Infection and Immunity, Suzhou
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3
College of Pharmaceutical Sciences, Suzhou
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4
The Third Affiliated Hospital of Soochow University, Changzhou
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Soochow University, Jiangsu 215123, China
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5
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of Medical Sciences and Peking Union Medical College, Beijing 10005; Suzhou
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Institute of Systems Medicine, Jiangsu 215123, China
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6
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Innovation Center for Structural Biology, Tsinghua University, Beijing 10084, China
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7
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*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
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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.
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SUMMARY
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ACE2 is a major receptor for cell entry of SARS-CoV-2. Despite advances in
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targeting ACE2 to inhibit SARS-CoV-2's binding, how to efficiently and flexibly
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control ACE2 levels for prevention of SARS-CoV-2 infection has not been
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explored. Here, we revealed Vitamin C (VitC) administration as an effective
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strategy to prevent SARS-CoV-2 infection. VitC reduced ACE2 protein levels in
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a dose-dependent manner, while partial reduction of ACE2 can greatly restrict
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SARS-CoV-2 infection. Further studies uncovered that USP50 is a crucial
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regulator of ACE2 protein levels, and VitC blocks the USP50-ACE2 interaction,
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thus promoting K48-linked polyubiquitination at Lys788 and degradation of
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ACE2, without disrupting ACE2 transcriptional expression. Importantly, VitC
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administration reduced host ACE2 and largely blocked SARS-CoV-2 infection
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in mice. This study identified an in vivo ACE2 balance controlled by both
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USP50 and an essential nutrient VitC, and revealed a critical role and
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application of VitC in daily protection from SARS-CoV-2 infection.
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Highlights
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VitC reduces ACE2 protein levels in a dose-dependent manner
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VitC and USP50 regulate K48-linked ubiquitination at Lys788 of ACE2
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VitC blocks the interaction between USP50 and ACE2
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VitC administration lowers host ACE2 and prevents SARS-CoV-2 infection
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in vivo
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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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