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Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination

Đukić et al., Frontiers in Bioscience-Landmark, doi:10.31083/j.fbl2801008
Jan 2023  
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Vitamin C for COVID-19
7th treatment shown to reduce risk in September 2020
*, now known with p = 0.000000098 from 67 studies, recognized in 10 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments.
In Vitro study showing inhibition of SARS-CoV-2 Mpro with vitamin C, L-arginine, and improved inhibition with the combination of both.
12 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 function EFSA, Galmés, Galmés (B). 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 3CLpro Malla, Đukić and inhibits SARS-CoV-2 infection by reducing ACE2 levels in a dose-dependent manner Zuo. Intracellular levels of vitamin C decline during COVID-19 hospitalization suggesting ongoing utilization and depletion of vitamin C Boerenkamp. 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 C Albóniga. 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 functioning Graydon, Vojdani.
Đukić et al., 13 Jan 2023, peer-reviewed, 9 authors. Contact: (corresponding author).
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperVitamin CAll
Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination
Ivana Đukić, Nevena Kaličanin, Milan Sencanski, Snezana B Pajovic, Jelena Milicevic, Jelena Prljic, Slobodan Paessler, Radivoje Prodanović, Sanja Glisic
Frontiers in Bioscience-Landmark, doi:10.31083/j.fbl2801008
Background: Drug resistance is a critical problem in health care that affects therapy outcomes and requires new approaches to drug design. SARS-CoV-2 M pro mutations are of concern as they can potentially reduce therapeutic efficacy. Viral infections are amongst the many disorders for which nutraceuticals have been employed as an adjunct therapy. The aim of this study was to examine the potential in vitro activity of L-arginine and vitamin C against SARS-CoV-2 M pro . Methods: The M pro inhibition assay was developed by cloning, expression, purification, and characterization of M pro . Selected compounds were then screened for protease inhibition. Results: Larginine was found to be active against SARS-CoV-2 M pro , while a vitamin C/L-arginine combination had a synergistic antiviral action against M pro . These findings confirm the results of our previous in silico repurposing study that showed L-arginine and vitamin C were potential M pro inhibitors. Moreover, they suggest a possible molecular mechanism to explain the beneficial effect of arginine in COVID patients. Conclusions: The findings of the current study are important because they help to identify COVID-19 treatments that are efficient, inexpensive, and have a favorable safety profile. The results of this study also suggest a possible adjuvant nutritional strategy for COVID-19 that could be used in conjunction with pharmacological agents.
Author Contributions Conceptualization-RP, SP and SG; performed the experiments-RP, NK, and IĐ; validation-NK, and RP; analyzed the data-NK, IĐ, MS, and RP; investigation-NK, IĐ, and MS; resources-RP; writing, original draft preparation-RP, SG, MS, SBP, JM and JP; writing, review and editing-SG, SBP, MS, SP and RP; visualization-IĐ, NK, RP; supervision-RP; project administration-RP, SG, JM, and MS. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. Ethics Approval and Consent to Participate Not applicable. Conflict of Interest The authors declare no conflict of interest.
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