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A study on the effect of natural products against the transmission of B.1.1.529 Omicron

Alkafaas et al., Virology Journal, doi:10.1186/s12985-023-02160-6

Aug 2023

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Vitamin C for COVID-19

6th treatment shown to reduce risk in September 2020

^*, now with p = 0.000000028 from 72 studies, recognized in 12 countries.

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

No treatment is 100% effective. Protocols combine treatments. ^* >10% efficacy, ≥3 studies.

4,500+ studies for 81 treatments. c19early.org

Review of natural products for SARS-CoV-2 omicron including an In Silico study showing quercetin, curcumin, ascorbic acid, nigellidine, and chloroquine among many compounds docked to the ACE2 metallopeptidase domain. Quercetin, curcumin, and ascorbic acid bound ACE2 with energy scores of -16.51, -13.5, and -12.55 kcal/mol. Nigellidine and chloroquine bound with lower affinity (-11.73 and -10.33 kcal/mol). The results suggest these compounds may have potential to inhibit SARS-CoV-2 infection by binding the ACE2 receptor.

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

6 In Silico studies1-6

6 In Vitro studies5,7-11

1 In Vivo animal study9

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 3CL^pro5,8 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.

Important missing comments or errors? Let us know.

Study covers quercetin, curcumin, nigella sativa, vitamin C, and HCQ.

1. Agamah et al., Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for COVID-19 disease phases, ScienceOpen, doi:10.58647/DRUGARXIV.PR000010.v1.scienceopen.com, doi.org.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

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. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

Alkafaas et al., 25 Aug 2023, peer-reviewed, 12 authors. Contact: samar.alkafas@science.tanta.edu.eg, samarsamy2017@yahoo.com, ghoshs@ufs.ac.za, soumyaghosh@yahoo.com, h.onyeaka@bham.ac.uk.

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

This Paper Vitamin C All

A study on the effect of natural products against the transmission of B.1.1.529 Omicron

Samar Sami Alkafaas, Abanoub Mosaad Abdallah, Aya Misbah Hussien, Heba Bedair, Mahmoud Abdo, Soumya Ghosh, Sara Samy Elkafas, Wilgince Apollon, Morteza Saki, Samah A Loutfy, Helen Onyeaka, Mohamed Hessien

Virology Journal, doi:10.1186/s12985-023-02160-6

Background The recent outbreak of the Coronavirus pandemic resulted in a successful vaccination program launched by the World Health Organization. However, a large population is still unvaccinated, leading to the emergence of mutated strains like alpha, beta, delta, and B.1.1.529 (Omicron). Recent reports from the World Health Organization raised concerns about the Omicron variant, which emerged in South Africa during a surge in COVID-19 cases in November 2021. Vaccines are not proven completely effective or safe against Omicron, leading to clinical trials for combating infection by the mutated virus. The absence of suitable pharmaceuticals has led scientists and clinicians to search for alternative and supplementary therapies, including dietary patterns, to reduce the effect of mutated strains. Main body This review analyzed Coronavirus aetiology, epidemiology, and natural products for combating Omicron. Although the literature search did not include keywords related to in silico or computational research, in silico investigations were emphasized in this study. Molecular docking was implemented to compare the interaction between natural products and Chloroquine with the ACE2 receptor protein amino acid residues of Omicron. The global Omicron infection proceeding SARS-CoV-2 vaccination was also elucidated. The docking results suggest that DGCG may bind to the ACE2 receptor three times more effectively than standard chloroquine. Conclusion The emergence of the Omicron variant has highlighted the need for alternative therapies to reduce the impact of mutated strains. The current review suggests that natural products such as DGCG may be effective in binding to the ACE2 receptor and combating the Omicron variant, however, further research is required to validate the results of this study and explore the potential of natural products to mitigate COVID-19. Highlights • There are 32 mutations in the spike of the Omicron variant. • Non-SARS-COV-2 vaccinated individuals accelerate transmission of Omicron variant.

Declarations Ethics approval and consent to participate Not applicable. Consent for publication All the authors read and agreed to publish this article. Competing interests The authors declare that they have no competing interests. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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{ 'indexed': {'date-parts': [[2024, 2, 6]], 'date-time': '2024-02-06T18:28:03Z', 'timestamp': 1707244083411}, 'reference-count': 221, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2023, 8, 25]], 'date-time': '2023-08-25T00:00:00Z', 'timestamp': 1692921600000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2023, 8, 25]], 'date-time': '2023-08-25T00:00:00Z', 'timestamp': 1692921600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'funder': [ { 'name': 'The Science, Technology & Innovation Funding Authority (STDF) in cooperation with ' 'the Egyptian Knowledge Bank'}, {'DOI': '10.13039/501100007950', 'name': 'Tanta University', 'doi-asserted-by': 'crossref'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': 'Abstract\n' ' Background\n' ' The recent outbreak of the Coronavirus pandemic resulted in a ' 'successful vaccination program launched by the World Health Organization. However, a large ' 'population is still unvaccinated, leading to the emergence of mutated strains like alpha, ' 'beta, delta, and B.1.1.529 (Omicron). Recent reports from the World Health Organization ' 'raised concerns about the Omicron variant, which emerged in South Africa during a surge in ' 'COVID-19 cases in November 2021. Vaccines are not proven completely effective or safe against ' 'Omicron, leading to clinical trials for combating infection by the mutated virus. The absence ' 'of suitable pharmaceuticals has led scientists and clinicians to search for alternative and ' 'supplementary therapies, including dietary patterns, to reduce the effect of mutated ' 'strains.\n' ' \n' ' Main body\n' ' This review analyzed Coronavirus aetiology, epidemiology, and natural ' 'products for combating Omicron. Although the literature search did not include keywords ' 'related to in silico or computational research, in silico investigations were emphasized in ' 'this study. Molecular docking was implemented to compare the interaction between natural ' 'products and Chloroquine with the ACE2 receptor protein amino acid residues of Omicron. The ' 'global Omicron infection proceeding SARS-CoV-2 vaccination was also elucidated. The docking ' 'results suggest that DGCG may bind to the ACE2 receptor three times more effectively than ' 'standard chloroquine.\n' ' \n' ' Conclusion\n' ' The emergence of the Omicron variant has highlighted the need for ' 'alternative therapies to reduce the impact of mutated strains. The current review suggests ' 'that natural products such as DGCG may be effective in binding to the ACE2 receptor and ' 'combating the Omicron variant, however, further research is required to validate the results ' 'of this study and explore the potential of natural products to mitigate COVID-19.\n' ' \n' ' Graphical abstract\n' ' \n' ' ', 'DOI': '10.1186/s12985-023-02160-6', 'type': 'journal-article', 'created': {'date-parts': [[2023, 8, 25]], 'date-time': '2023-08-25T06:02:14Z', 'timestamp': 1692943334000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 3, 'title': 'A study on the effect of natural products against the transmission of B.1.1.529 Omicron', 'prefix': '10.1186', 'volume': '20', 'author': [ {'given': 'Samar Sami', 'family': 'Alkafaas', 'sequence': 'first', 'affiliation': []}, {'given': 'Abanoub Mosaad', 'family': 'Abdallah', 'sequence': 'additional', 'affiliation': []}, {'given': 'Aya Misbah', 'family': 'Hussien', 'sequence': 'additional', 'affiliation': []}, {'given': 'Heba', 'family': 'Bedair', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mahmoud', 'family': 'Abdo', 'sequence': 'additional', 'affiliation': []}, {'given': 'Soumya', 'family': 'Ghosh', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sara Samy', 'family': 'Elkafas', 'sequence': 'additional', 'affiliation': []}, {'given': 'Wilgince', 'family': 'Apollon', 'sequence': 'additional', 'affiliation': []}, {'given': 'Morteza', 'family': 'Saki', 'sequence': 'additional', 'affiliation': []}, {'given': 'Samah A.', 'family': 'Loutfy', 'sequence': 'additional', 'affiliation': []}, {'given': 'Helen', 'family': 'Onyeaka', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mohamed', 'family': 'Hessien', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2023, 8, 25]]}, 'reference': [ { 'key': '2160_CR1', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.12998/wjcc.v10.i1.1', 'volume': '10', 'author': 'S-Y Ren', 'year': '2022', 'unstructured': 'Ren S-Y, Wang W-B, Gao R-D, Zhou A-M. 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' 'Binding of a natural anthocyanin inhibitor to influenza neuraminidase by ' 'mass spectrometry. Anal Bioanal Chem. 2013;405:6563–72.', 'journal-title': 'Anal Bioanal Chem'}], 'container-title': 'Virology Journal', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12985-023-02160-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1186/s12985-023-02160-6/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12985-023-02160-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 11, 18]], 'date-time': '2023-11-18T22:18:41Z', 'timestamp': 1700345921000}, 'score': 1, 'resource': {'primary': {'URL': 'https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02160-6'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 8, 25]]}, 'references-count': 221, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2023, 12]]}}, 'alternative-id': ['2160'], 'URL': 'http://dx.doi.org/10.1186/s12985-023-02160-6', 'relation': {}, 'ISSN': ['1743-422X'], 'subject': ['Infectious Diseases', 'Virology'], 'container-title-short': 'Virol J', 'published': {'date-parts': [[2023, 8, 25]]}, 'assertion': [ { 'value': '29 March 2023', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '15 August 2023', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '25 August 2023', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'Not applicable.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}, { 'value': 'All the authors read and agreed to publish this article.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}}, { 'value': 'The authors declare that they have no competing interests.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '191'}

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