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All Studies   Meta Analysis    Recent:   

Vitamin C inhibits SARS coronavirus-2 main protease essential for viral replication

Malla et al., bioRxiv, doi:10.1101/2021.05.02.442358
May 2021  
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Vitamin C for COVID-19
6th treatment shown to reduce risk in September 2020
 
*, now with p = 0.000000038 from 71 studies, recognized in 12 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 77 treatments. c19early.org
In SIlico and In Vitro study showing that vitamin C inhibits SARS-CoV-2 3CLpro. Authors note that the different clinical results may be explained in part by the widely varying dosages used, and they conclude that vitamin C and/or derivatives may become an important treatment for COVID-19 and other viral infections.
13 preclinical studies support the efficacy of vitamin C for COVID-19:
Vitamin C has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function12-14. 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. Vitamin C inhibits SARS-CoV-2 3CLpro5,8 and inhibits SARS-CoV-2 infection by reducing ACE2 levels in a dose-dependent manner9. Intracellular levels of vitamin C decline during COVID-19 hospitalization suggesting ongoing utilization and depletion of vitamin C15. Threonic acid, a metabolite of vitamin C, is lower in mild and severe cases, 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 C16. Symptomatic COVID-19 is associated with a lower frequency of natural killer (NK) cells, and vitamin C has been shown to improve NK cell numbers and functioning17,18.
Malla et al., 3 May 2021, preprint, 9 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperVitamin CAll
Vitamin C Binds to SARS Coronavirus-2 Main Protease Essential for Viral Replication
Tek Narsingh Malla, Suraj Pandey, Luis Aldama, Dennisse Feliz, Moraima Noda, Ishwor Poudyal, George N Phillips Jr, Emina A Stojković, Marius Schmidt
doi:10.1101/2021.05.02.442358
There is an urgent need for anti-viral agents that treat and/or prevent Covid-19 caused by SARS-Coronavirus (CoV-2) infections. The replication of the SARS CoV-2 is dependent on the activity of two cysteine proteases, a papain-like protease, PL-pro, and the 3C-like protease known as main protease Mpro or 3CLpro. The shortest and the safest path to clinical use is the repurposing of drugs with binding affinity to PLpro or 3CLpro that have an established safety profile in humans. Several studies have reported crystal structures of SARS-CoV-2 main protease in complex with FDA approved drugs such as those used in treatment of hepatitis C. Here, we report the crystal structure of 3CLpro in complex Vitamin C (L-ascorbate) bound to the protein's active site at 2.5 Ångstrom resolution. The crystal structure of the Vitamin C 3CLpro complex may aid future studies on the effect of Vitamin C not only on the coronavirus main protease but on related proteases of other infectious viruses.
Supplementary Material Expression. The CoV-2 3CLpro sequence was synthetized (GenScript) for optimized expression in E. coli according to sequence information published previously (Zhang, Lin, Sun, et al., 2020) . In short, the N-terminus of 3CLpro is fused to glutathione-S-transferase (GST). It further has a 6-His tag at the c-terminus. The N-terminal GST will be autocatalytically cleaved off after expression due to an engineered 3CLpro cleavage sequence. Although the His tag can be cleaved off by a PreScission protease, the tag did not interfere with crystallization and consequently was left on. Overexpression and protein purification protocols were modified from previous reports. E. coli were grown to 0.8 OD 600 at 37 o in terrific broth. Expression was induced by 1 mmol/L IPTG at 25 o C. After 3 h of expression, the culture was induced a second time (1 mmol/L IPTG), and shaken overnight at 20 o C. The yield is about 80 mg for a 6 L culture. Cells were resuspended in lysis buffer (20mM Tris Base, 150 mmol/L NaCl, pH 7.8.). After lysis of the bacterial cells, debris was centrifuged at 50,000 g for 1 hour. The lysate was let stand at room temperature for 3 h (overnight is also possible). After this, the lysate was pumped through a column containing 15 mL of Talon Cobalt resin (TAKARA). The resin was washed without using imidazole using a wash cycle consisting of low salt (20 mmol/L Tris Base, 50 mmol/L NaCl, pH 7.8), high salt (20 mmol/L Tris Base, 1 mol/L NaCl, pH 7.8) and..
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