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c19early.org COVID-19 treatment researchVitamin CVitamin C (more..)
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Phytochemical Inhibitors of SARS‐CoV‐2 Entry: Targeting the ACE2‐RBD Interaction with l‐Tartaric Acid, l‐Ascorbic Acid, and Curcuma longa Extract

Najimi et al., ChemistrySelect, doi:10.1002/slct.202406035, Apr 2025
https://c19early.org/najimic.html
Vitamin C for COVID-19
6th treatment shown to reduce risk in September 2020, now with p = 0.00000004 from 74 studies, recognized in 22 countries.
Lower risk for mortality, ICU, hospitalization, and recovery.
No treatment is 100% effective. Protocols combine treatments.
5,700+ studies for 135 treatments. c19early.org
In Vitro and In Silico study showing that l-tartaric acid, l-ascorbic acid, and Curcuma longa extract (curcumin, demethoxycurcumin, bisdemethoxycurcumin) inhibit the SARS-CoV-2 spike RBD interaction with human ACE2. Authors demonstrate by competitive ELISA that l-tartaric acid is most potent (IC₅₀ ≈ 0.009 mg mL⁻¹), l-ascorbic acid reaches half-maximal inhibition at ≈ 0.213 mg mL⁻¹, while C. longa extract shows dose-dependent blockade with IC₅₀ ≈ 0.779 mg mL⁻¹. Molecular docking and 100 ns MD simulations reveal stable hydrogen-bond and hydrophobic networks with ACE2.
16 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 function14-16. 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 3CLpro6,10, inhibits SARS-CoV-2 infection by reducing ACE2 levels in a dose-dependent manner11, and may limit COVID-19 induced cardiac damage by acting as an antioxidant and potentially reducing the reactive oxygen species (ROS) production induced by the spike protein that contributes to the activation of profibrotic pathways8. Vitamin C reduces inflammation, oxidative stress, and NETosis, supporting immune function and vascular protection17. Intracellular levels of vitamin C decline during COVID-19 hospitalization suggesting ongoing utilization and depletion of vitamin C18. 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 C19. 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 functioning20,21.
Study covers curcumin and vitamin C.
Najimi et al., 28 Apr 2025, peer-reviewed, 10 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
DOI record: { "DOI": "10.1002/slct.202406035", "ISSN": [ "2365-6549", "2365-6549" ], "URL": "http://dx.doi.org/10.1002/slct.202406035", "abstract": "<jats:title>Abstract</jats:title><jats:p>Phytochemicals are emerging as promising antiviral agents with the potential to address both acute and long‐term complications of viral infections such as COVID‐19. SARS‐CoV‐2, the virus responsible for COVID‐19, enters host cells by binding its spike protein's receptor‐binding domain (RBD) to the angiotensin‐converting enzyme‐2 (ACE2) receptor. Inhibiting this interaction may provide new therapeutic approaches. This study aimed to evaluate the inhibitory effects of <jats:italic>Curcuma longa</jats:italic> extract, <jats:sc>l</jats:sc>‐ascorbic acid, and <jats:sc>l</jats:sc>‐tartaric acid on the ACE2‐RBD interaction and to explore their potential as antiviral agents against SARS‐CoV‐2. A competitive ELISA was used to assess the inhibitory activity on the ACE2‐RBD interaction, with <jats:sc>l</jats:sc>‐tartaric acid showing the strongest inhibition (IC50 = 0.009 mg/ml). <jats:italic>C. longa</jats:italic> extract displayed dose‐dependent inhibition, while <jats:sc>l</jats:sc>‐ascorbic acid showed peak inhibition between 0.4 and 1 mg/mL. Molecular docking and 100 ns molecular dynamics simulations confirmed strong and stable interactions involving curcuminoids with ACE2. These findings underscore the potential of these compounds to function as effective SARS‐CoV‐2 entry inhibitors, supporting their further investigation as promising therapeutic candidates.</jats:p>", "alternative-id": [ "10.1002/slct.202406035" ], "assertion": [ { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Received", "name": "received", "order": 0, "value": "2024-12-20" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "2025-04-13" }, { "group": { "label": "Publication History", "name": "publication_history" }, "label": "Published", "name": "published", "order": 3, "value": "2025-04-28" } ], "author": [ { "ORCID": "https://orcid.org/0009-0008-5536-0237", "affiliation": [ { "name": "Laboratory of Human Pathologies Biology, Faculty of Sciences Mohammed V University Rabat Morocco" }, { "name": "Mohammed VI University of Sciences and Health (UM6SS) Casablanca Morocco" }, { "name": "Mohammed VI Center for Research and Innovation (CM6RI) Rabat Morocco" } ], "authenticated-orcid": false, "family": "Najimi", "given": "Nouhaila", "sequence": "first" }, { "affiliation": [ { "name": "Department of Biology Faculty of Sciences Dhar El Mahraz Sidi Mohammed Ben Abdellah University Fez 30003 Morocco" } ], "family": "Amssayef", "given": "Ayoub", "sequence": "additional" }, { "affiliation": [ { "name": "Team of Ethnopharmacology and Pharmacognosy, Faculty of Sciences and Techniques Errachidia Moulay Ismail University of Meknes BP 509, Boutalamine Errachidia 52000 Morocco" }, { "name": "Center of Genomic of Human Pathologies Biology Faculty of Medicine Mohammed V University Rabat Morocco" } ], "family": "Bouadid", "given": "Ismail", "sequence": "additional" }, { "affiliation": [ { "name": "Mohammed VI University of Sciences and Health (UM6SS) Casablanca Morocco" }, { "name": "Mohammed VI Center for Research and Innovation (CM6RI) Rabat Morocco" } ], "family": "Hakmi", "given": "Mohammed", "sequence": "additional" }, { "affiliation": [ { "name": "Mohammed VI University of Sciences and Health (UM6SS) Casablanca Morocco" }, { "name": "Mohammed VI Center for Research and Innovation (CM6RI) Rabat Morocco" } ], "family": "Festali", "given": "Rihab", "sequence": "additional" }, { "affiliation": [ { "name": "Mohammed VI University of Sciences and Health (UM6SS) Casablanca Morocco" }, { "name": "Mohammed VI Center for Research and Innovation (CM6RI) Rabat Morocco" }, { "name": "Laboratory of Biology and Health, Faculty of Sciences of Tétouan Abdelmalek Essaâdi University Tétouan Morocco" } ], "family": "Kadi", "given": "Chaimae", "sequence": "additional" }, { "affiliation": [ { "name": "Higher Institute of Nursing Professions and Health Techniques Rabat Morocco" } ], "family": "Seghrouchni", "given": "Fouad", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Human Pathologies Biology, Faculty of Sciences Mohammed V University Rabat Morocco" }, { "name": "Team of Ethnopharmacology and Pharmacognosy, Faculty of Sciences and Techniques Errachidia Moulay Ismail University of Meknes BP 509, Boutalamine Errachidia 52000 Morocco" }, { "name": "Center of Genomic of Human Pathologies Biology Faculty of Medicine Mohammed V University Rabat Morocco" } ], "family": "El hassani", "given": "Rabii Ameziane", "sequence": "additional" }, { "affiliation": [ { "name": "Team of Ethnopharmacology and Pharmacognosy, Faculty of Sciences and Techniques Errachidia Moulay Ismail University of Meknes BP 509, Boutalamine Errachidia 52000 Morocco" }, { "name": "Center of Genomic of Human Pathologies Biology Faculty of Medicine Mohammed V University Rabat Morocco" } ], "family": "Eddouks", "given": "Mohamed", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Human Pathologies Biology, Faculty of Sciences Mohammed V University Rabat Morocco" }, { "name": "Team of Ethnopharmacology and Pharmacognosy, 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