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Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E

Moatasim et al., Microorganisms, doi:10.3390/microorganisms11112777

Nov 2023

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Vitamin C for COVID-19

6th treatment shown to reduce risk in September 2020

^*, now known with p = 0.000000087 from 70 studies, recognized in 11 countries.

Lower risk for mortality, ICU admission, hospitalization, and recovery.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,100+ studies for 60+ treatments. c19early.org

In Vitro and In Silico analysis finding that methylcobalamin, hydroxocobalamin, and cyanocobalamin forms of vitamin B12 showed broad-spectrum inhibition against SARS-CoV-2, MERS-CoV, and HCoV-229E. Methylcobalamin had the highest activity against SARS-CoV-2, hydroxocobalamin against MERS-CoV, and cyanocobalamin against HCoV-229E. Vitamin B9 also reduced viral RNA levels of all three coronaviruses in infected cells. In silico analyses predict that vitamin B12 and B9 bind and interfere with viral proteins and receptors. The results suggest that vitamin B12, especially methylcobalamin, and vitamin B9 may have potential benefits for COVID-19 patients. Positive results were also found for other B vitamins and vitamins A, C, D, and K, with varying IC₅₀ and SI.

12 preclinical studies support the efficacy of vitamin C for COVID-19:

5 In Silico studies Alkafaas, Kumar, Malla, Morales-Bayuelo, Pandya

6 In Vitro studies Goc, Hajdrik, Malla, Moatasim, Zuo, Đukić

1 In Vivo animal study Zuo

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 3CL^pro 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.

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Study covers vitamin B12, vitamin B9, vitamin A, vitamin C, and vitamin D.

1. Albóniga et al., Differential abundance of lipids and metabolites related to SARS-CoV-2 infection and susceptibility, Scientific Reports, doi:10.1038/s41598-023-40999-5.nature.com, doi.org.

2. Alkafaas et al., A study on the effect of natural products against the transmission of B.1.1.529 Omicron, Virology Journal, doi:10.1186/s12985-023-02160-6.biomedcentral.com, doi.org.

3. Boerenkamp et al., Low Levels of Serum and Intracellular Vitamin C in Hospitalized COVID-19 Patients, Nutrients, doi:10.3390/nu15163653.mdpi.com, doi.org.

4. Đukić et al., Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination, Frontiers in Bioscience-Landmark, doi:10.31083/j.fbl2801008.imrpress.com, doi.org.

5. EFSA, Scientific Opinion on the substantiation of health claims related to vitamin C and protection of DNA, proteins and lipids from oxidative damage (ID 129, 138, 143, 148), antioxidant function of lutein (ID 146), maintenance of vision (ID 141, 142), collagen formation (ID 130, 131, 136, 137, 149), function of the nervous system (ID 133), function of the immune system (ID 134), function of the immune system during and after extreme physical exercise (ID 144), non-haem iron absorption (ID 132, 147), energy-yielding metabolism (ID 135), and relief in case of irritation in the upper respiratory tract (ID 1714, 1715) pursuant to Article 13(1) of Regulation (EC) No 1924/2006, EFSA Journal, doi:10.2903/j.efsa.2009.1226.europa.eu, doi.org.

6. Galmés et al., Suboptimal Consumption of Relevant Immune System Micronutrients Is Associated with a Worse Impact of COVID-19 in Spanish Populations, Nutrients, doi:10.3390/nu14112254.mdpi.com, doi.org.

7. Galmés (B) et al., Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework, Nutrients, doi:10.3390/nu12092738.mdpi.com, doi.org.

8. Goc et al., Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants, European Journal of Microbiology and Immunology, doi:10.1556/1886.2021.00022.akjournals.com, doi.org.

9. Graydon et al., High baseline frequencies of natural killer cells are associated with asymptomatic SARS-CoV-2 infection, Current Research in Immunology, doi:10.1016/j.crimmu.2023.100064.sciencedirect.com, doi.org.

10. Hajdrik et al., In Vitro Determination of Inhibitory Effects of Humic Substances Complexing Zn and Se on SARS-CoV-2 Virus Replication, Foods, doi:10.3390/foods11050694.mdpi.com, doi.org.

11. Kumar et al., In silico virtual screening-based study of nutraceuticals predicts the therapeutic potentials of folic acid and its derivatives against COVID-19, VirusDisease, doi:10.1007/s13337-020-00643-6.springer.com, doi.org.

12. Malla et al., Vitamin C inhibits SARS coronavirus-2 main protease essential for viral replication, bioRxiv, doi:10.1101/2021.05.02.442358.biorxiv.org, doi.org.

13. Moatasim et al., Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E, Microorganisms, doi:10.3390/microorganisms11112777.mdpi.com, doi.org.

14. Morales-Bayuelo et al., New findings on ligand series used as SARS-CoV-2 virus inhibitors within the frameworks of molecular docking, molecular quantum similarity and chemical reactivity indices, F1000Research, doi:10.12688/f1000research.123550.3.f1000research.com, doi.org.

15. Pandya et al., Unravelling Vitamin B12 as a potential inhibitor against SARS-CoV-2: A computational approach, Informatics in Medicine Unlocked, doi:10.1016/j.imu.2022.100951.sciencedirect.com, doi.org.

16. Vojdani et al., In vivo effect of ascorbic acid on enhancement of human natural killer cell activity, Nutrition Research, doi:10.1016/S0271-5317(05)80799-7.sciencedirect.com, doi.org.

17. Zuo et al., Vitamin C promotes ACE2 degradation and protects against SARS‐CoV‐2 infection, EMBO reports, doi:10.15252/embr.202256374.wiley.com, doi.org.

Moatasim et al., 15 Nov 2023, peer-reviewed, 13 authors. Contact: mohamedahmedali2004@yahoo.com (corresponding author), yasmin.moatasim@human-link.org, omnia.abdelaziz@human-link.org, mokhtar.rizk@human-link.org, mohameddiaaelsayes@outlook.com, mina@human-link.org, gaballah09@gmail.com, ahmed_nrc2000@hotmail.com, rabeh.elshesheny@human-link.org, dr.ahmed.mamdouh.93@gmail.com, faten.okda@stjude.org, ghazi@human-link.org, ahmed.kandeil@human-link.org.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Vitamin C All

Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E

Yassmin Moatasim, Omnia Kutkat, Ahmed M Osman, Mokhtar R Gomaa, Faten Okda, Mohamed El Sayes, Mina Nabil Kamel, Mohamed Gaballah, Ahmed Mostafa, Rabeh El-Shesheny, Ghazi Kayali, Mohamed A Ali, Ahmed Kandeil

Microorganisms, doi:10.3390/microorganisms11112777

Repurposing vitamins as antiviral supporting agents is a rapid approach used to control emerging viral infections. Although there is considerable evidence supporting the use of vitamin supplementation in viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the specific role of each vitamin in defending against coronaviruses remains unclear. Antiviral activities of available vitamins on the infectivity and replication of human coronaviruses, namely, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus 229E (HCoV-229E), were investigated using in silico and in vitro studies. We identified potential broad-spectrum inhibitor effects of Hydroxocobalamin and Methylcobalamin against the three tested CoVs. Cyanocobalamin could selectively affect SARS-CoV-2 but not MERS-CoV and HCoV-229E. Methylcobalamin showed significantly higher inhibition values on SARS-CoV-2 compared with Hydroxocobalamin and Cyanocobalamin, while Hydroxocobalamin showed the highest potent antiviral activity against MERS-CoV and Cyanocobalamin against HCoV-229E. Furthermore, in silico studies were performed for these promising vitamins to investigate their interaction with SARS-CoV-2, MERS-CoV, and HCoV-229E viral-specific cell receptors (ACE2, DPP4, and hAPN protein, respectively) and viral proteins (S-RBD, 3CL pro, RdRp), suggesting that Hydroxocobalamin, Methylcobalamin, and Cyanocobalamin may have significant binding affinity to these proteins. These results show that Methylcobalamin may have potential benefits for coronavirus-infected patients.

Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/microorganisms11112777/s1, Figure S1 : antiviral activities of B-Com against SARS-CoV-2, and MERS-CoV by plaque reduction assay; Table S1 : Binding energies (as Docking and Glide scores) of the tested vitamins against RBD and spike proteins correlated with the three coronaviruses; Table S2 : Binding energies (as Docking and Glide scores) of the tested vitamins against 3C-like protease (3CLpro) or main protease correlated with the three coronaviruses; Table S3 : Binding energies (as Docking and Glide scores) of the tested vitamins against RNA dependent RNA polymerase (RdRp)correlated with the three coronaviruses; Tables S4: Binding energies (as Docking and Glide scores) of the tested vitamins against human cell receptors correlated with the three coronaviruses. Conflicts of Interest: The authors declare no conflict of interest.

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