Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E
Abstract
:1. Introduction
2. Materials and Methods
2.1. In Vitro Cytotoxicity and Inhibitory Activity against SARS-CoV-2 Virus
2.1.1. Vitamins and Test Viruses
2.1.2. Determination of In Vitro Cytotoxic Concentration 50% (CC50) and Antiviral Inhibitory Concentration 50% (IC50)
2.2. In Silico Analysis
2.2.1. Ligand Preparation
2.2.2. In Silico 3D Structure Protein Preparation
2.2.3. Molecular Docking
2.3. Quantitative Real-Time RT-PCR Assessment of RNA Expression after Treatment
2.4. Antiviral Activity Using Plaque Reduction Assay
virus with treatment)/(count of plaques in virus control) × 100
2.5. In Vitro Mechanism of Action
2.5.1. Viral Adsorption Mechanism
2.5.2. Viral Replication Mechanism
2.5.3. Neutralization Mechanism
2.6. Statistical Analysis
3. Results
3.1. Cytotoxicity and Inhibitory Activity of Reference Vitamins against Coronaviruses
3.2. Titration of Viral RNA Inhibition Percentage Using qRT-PCR after Treatment
3.3. Protein Assembly and Preparation for Docking
3.4. Molecular Docking
3.4.1. Spike Proteins
3.4.2. 3CL (M-Protease)
3.4.3. Cell Receptors
3.4.4. RNA-Dependent RNA Polymerase (RdRP) Proteins
3.5. Plaque Reduction Assay
3.6. Analyzing the Binding Capacity through Docking
3.6.1. Spike RBD and Cell Receptors
3.6.2. RNA-Dependent RNA Polymerase
3.6.3. 3CL Protease
3.7. In Vitro Mechanism of Action
4. Discussion
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Chemical Name | Generic Name | CC50 | SARS-CoV-2 | MERS-CoV | HCoV-229E | |||
---|---|---|---|---|---|---|---|---|
IC50 | SI | IC50 | SI | IC50 | SI | |||
Retinyl Palmitate | A | 466.3 | 41.0 | 11.4 | 125.0 | 3.7 | 345.9 | 1.3 |
Thiamine HCL | B1 | 580.3 | 52.0 | 11.2 | 128.7 | 4.5 | 79.5 | 7.3 |
Benfotiamine (Thiamine) | B1 | 509.1 | 18.6 | 27.3 | 387.1 | 1.3 | 525.5 | 1.0 |
Riboflavin Phosphate | B2 | 848.2 | 37.4 | 22.7 | 208.0 | 4.1 | 14.8 | 57.5 |
Niacinamide (niacin) | B3 | 1052.0 | 26.9 | 39.2 | 219.7 | 4.8 | 35.6 | 29.5 |
Pantothenic Acid | B5 | 2316.0 | 917.8 | 2.5 | 55.1 | 42.0 | 158.3 | 14.6 |
Pyridoxal | B6 | 523.1 | 110.6 | 4.7 | 267.2 | 2.0 | 9.6 | 54.5 |
Biotin | B7 | 575.4 | 129.1 | 4.5 | 317.3 | 1.8 | >CC50 | 0 |
Folic acid | B9 | 349.5 | 110.5 | 3.2 | >CC50 | 0 | 330.6 | 1.1 |
Hydroxycobalamin | B12 | 631.1 | 17.0 | 37.1 | 21.5 | 29.3 | 26.1 | 24.2 |
Methylcobalamin | B12 | 393.7 | 12.0 | 32.9 | 6.0 | 65.4 | 29.7 | 13.3 |
Cyanocobalamin | B12 | 246.9 | 13.1 | 18.9 | 29.6 | 8.3 | 104.2 | 2.4 |
Ascorbic Acid | C | 570.5 | 168.4 | 3.4 | 165.4 | 3.4 | 81.8 | 7.0 |
Ergocalciferol | D2 | 73.4 | 5.4 | 13.5 | 14.6 | 5.0 | 42.0 | 1.7 |
Chlolecalciferol | D3 | 170.8 | 29.8 | 5.7 | 38.6 | 4.4 | 33.9 | 5.0 |
a-Tocopheryl Acetate | E | 570.2 | 122.3 | 4.7 | 104.5 | 5.5 | 127.9 | 4.5 |
Tocopherols | E | 566.8 | 106.0 | 5.3 | 36.0 | 15.7 | 286.4 | 2.0 |
Alpha lipoic Acid | a-lipoic Acid | 574.6 | 41.2 | 13.9 | 35.4 | 16.2 | 288.3 | 2.0 |
Phytomenadione | K1 | 1088.0 | 297.3 | 3.7 | 474.9 | 2.3 | 473.7 | 2.3 |
Menadione | K3 | 147.8 | 10.3 | 14.4 | 45.2 | 3.3 | 156.8 | 0.9 |
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Moatasim, Y.; Kutkat, O.; Osman, A.M.; Gomaa, M.R.; Okda, F.; El Sayes, M.; Kamel, M.N.; Gaballah, M.; Mostafa, A.; El-Shesheny, R.; 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 2023, 11, 2777. https://doi.org/10.3390/microorganisms11112777
Moatasim Y, Kutkat O, Osman AM, Gomaa MR, Okda F, El Sayes M, Kamel MN, Gaballah M, Mostafa A, El-Shesheny R, 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. 2023; 11(11):2777. https://doi.org/10.3390/microorganisms11112777
Chicago/Turabian StyleMoatasim, Yassmin, Omnia Kutkat, Ahmed M. Osman, Mokhtar R. Gomaa, Faten Okda, Mohamed El Sayes, Mina Nabil Kamel, Mohamed Gaballah, Ahmed Mostafa, Rabeh El-Shesheny, and et al. 2023. "Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E" Microorganisms 11, no. 11: 2777. https://doi.org/10.3390/microorganisms11112777
APA StyleMoatasim, Y., Kutkat, O., Osman, A. M., Gomaa, M. R., Okda, F., El Sayes, M., Kamel, M. N., Gaballah, M., Mostafa, A., El-Shesheny, R., Kayali, G., Ali, M. A., & Kandeil, A. (2023). Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E. Microorganisms, 11(11), 2777. https://doi.org/10.3390/microorganisms11112777