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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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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.
14 preclinical studies support the efficacy of vitamin B9 for COVID-19:
Vitamin B9 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 B9 inhibits SARS-CoV-2 In Silico3-11, reduces spike protein binding ability11, binds with the spike protein receptor binding domain for alpha and omicron variants2, inhibits the SARS-CoV-2 nucleocapsid protein3, inhibits 3CLpro and PLpro in enzymatic assays2, significantly reduces infection for alpha and omicron SARS-CoV-2 pseudoviruses2, and inhibits ACE2 expression and SARS-CoV-2 infection in a mouse model11.
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 B9All
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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