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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 D for COVID-19
8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 111 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.
23 preclinical studies support the efficacy of vitamin D for COVID-19:
Vitamin D has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function22-25. Vitamin D inhibits SARS-CoV-2 replication in vitro12,19, mitigates lung inflammation, damage, and lethality in mice with an MHV-3 model for β-CoV respiratory infections12,19, reduces SARS-CoV-2 replication in nasal epithelial cells via increased type I interferon expression15, downregulates proinflammatory cytokines IL-1β and TNF-α in SARS-CoV-2 spike protein-stimulated cells11, attenuates nucleocapsid protein-induced hyperinflammation by inactivating the NLRP3 inflammasome through the VDR-BRCC3 signaling pathway16, may be neuroprotective by protecting the blood-brain barrier, reducing neuroinflammation, and via immunomodulatory effects26, downregulates ACE2 and TMPRSS2 in human trophoblasts and minimizes spike protein-induced inflammation14, minimizes platelet aggregation mediated by SARS-CoV-2 spike protein via inhibiting integrin αIIbβ3 outside-in signaling10, and improves regulatory immune cell levels and control of proinflammatory cytokines in severe COVID-1927. Calcifediol inhibits SARS-CoV-2 papain-like protease (PLpro), a critical enzyme for viral replication9. Symptomatic COVID-19 is associated with a lower frequency of natural killer (NK) cells and vitamin D has been shown to improve NK cell activity28,29.
Study covers vitamin B12, vitamin B9, vitamin A, vitamin C, and vitamin D.
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 PaperVitamin DAll
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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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.</jats:p>', 'DOI': '10.3390/microorganisms11112777', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 11, 15]], 'date-time': '2023-11-15T15:57:46Z', 'timestamp': 1700063866000}, 'page': '2777', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus ' '2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E', 'prefix': '10.3390', 'volume': '11', 'author': [ { 'ORCID': 'http://orcid.org/0000-0003-2159-2511', 'authenticated-orcid': False, 'given': 'Yassmin', 'family': 'Moatasim', 'sequence': 'first', 'affiliation': [ { 'name': 'Center of Scientific Excellence for Influenza Viruses, National ' 'Research Centre, Giza 12622, Egypt'}]}, { 'given': 'Omnia', 'family': 'Kutkat', 'sequence': 'additional', 'affiliation': [ { 'name': 'Center of Scientific Excellence for Influenza Viruses, National ' 'Research Centre, Giza 12622, Egypt'}]}, { 'ORCID': 'http://orcid.org/0000-0002-9004-751X', 'authenticated-orcid': False, 'given': 'Ahmed M.', 'family': 'Osman', 'sequence': 'additional', 'affiliation': [ { 'name': 'Biochemistry Department, Faculty of Science, Cairo University, ' 'Cairo 12613, Egypt'}]}, { 'given': 'Mokhtar R.', 'family': 'Gomaa', 'sequence': 'additional', 'affiliation': [ { 'name': 'Center of Scientific Excellence for Influenza Viruses, National ' 'Research Centre, Giza 12622, Egypt'}]}, { 'ORCID': 'http://orcid.org/0000-0001-6245-5391', 'authenticated-orcid': False, 'given': 'Faten', 'family': 'Okda', 'sequence': 'additional', 'affiliation': [ { 'name': 'Veterinary Research Institute, National Research Centre, Giza ' '12622, Egypt'}, { 'name': 'Department of Infectious Diseases, St. Jude Children’s Research ' 'Hospital, Memphis, TN 38105, USA'}]}, { 'given': 'Mohamed', 'family': 'El Sayes', 'sequence': 'additional', 'affiliation': [ { 'name': 'Center of Scientific Excellence for Influenza Viruses, National ' 'Research Centre, Giza 12622, Egypt'}]}, { 'given': 'Mina Nabil', 'family': 'Kamel', 'sequence': 'additional', 'affiliation': [ { 'name': 'Center of Scientific Excellence for Influenza Viruses, National ' 'Research Centre, Giza 12622, Egypt'}]}, { 'given': 'Mohamed', 'family': 'Gaballah', 'sequence': 'additional', 'affiliation': [ { 'name': 'Center of Scientific Excellence for Influenza Viruses, National ' 'Research Centre, Giza 12622, Egypt'}]}, { 'ORCID': 'http://orcid.org/0000-0002-2878-5714', 'authenticated-orcid': False, 'given': 'Ahmed', 'family': 'Mostafa', 'sequence': 'additional', 'affiliation': [ { 'name': 'Center of Scientific Excellence for Influenza Viruses, National ' 'Research Centre, Giza 12622, Egypt'}]}, { 'given': 'Rabeh', 'family': 'El-Shesheny', 'sequence': 'additional', 'affiliation': [ { 'name': 'Center of Scientific Excellence for Influenza Viruses, National ' 'Research Centre, Giza 12622, Egypt'}]}, { 'given': 'Ghazi', 'family': 'Kayali', 'sequence': 'additional', 'affiliation': [{'name': 'Human Link, Dubai 115738, United Arab Emirates'}]}, { 'ORCID': 'http://orcid.org/0000-0002-5615-3212', 'authenticated-orcid': False, 'given': 'Mohamed A.', 'family': 'Ali', 'sequence': 'additional', 'affiliation': [ { 'name': 'Center of Scientific Excellence for Influenza Viruses, National ' 'Research Centre, Giza 12622, Egypt'}]}, { 'ORCID': 'http://orcid.org/0000-0003-3253-6961', 'authenticated-orcid': False, 'given': 'Ahmed', 'family': 'Kandeil', 'sequence': 'additional', 'affiliation': [ { 'name': 'Center of Scientific Excellence for Influenza Viruses, National ' 'Research Centre, Giza 12622, Egypt'}]}], 'member': '1968', 'published-online': {'date-parts': [[2023, 11, 15]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'first-page': '533', 'DOI': '10.1016/S1473-3099(20)30120-1', 'article-title': 'An interactive web-based dashboard to track COVID-19 in real time', 'volume': '20', 'author': 'Dong', 'year': '2020', 'journal-title': 'Lancet Infect. 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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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