Pleiotropic Functions of Nitric Oxide Produced by Ascorbate for the Prevention and Mitigation of COVID-19: A Revaluation of Pauling’s Vitamin C Therapy

{ 'indexed': {'date-parts': [[2023, 2, 17]], 'date-time': '2023-02-17T05:36:16Z', 'timestamp': 1676612176610}, 'reference-count': 222, 'publisher': 'MDPI AG', 'issue': '2', 'license': [ { 'start': { 'date-parts': [[2023, 2, 3]], 'date-time': '2023-02-03T00:00:00Z', 'timestamp': 1675382400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>Linus Pauling, who was awarded the Nobel Prize in Chemistry, suggested that a high ' 'dose of vitamin C (l-ascorbic acid) might work as a prevention or treatment for the common ' 'cold. Vitamin C therapy was tested in clinical trials, but clear evidence was not found at ' 'that time. Although Pauling’s proposal has been strongly criticized for a long time, vitamin ' 'C therapy has continued to be tested as a treatment for a variety of diseases, including ' 'coronavirus infectious disease 2019 (COVID-19). The pathogen of COVID-19, SARS-CoV-2, belongs ' 'to the β-coronavirus lineage, which includes human coronavirus, severe acute respiratory ' 'syndrome (SARS), and Middle East respiratory syndrome (MERS). This review intends to shed new ' 'light on vitamin C antiviral activity that may prevent SARS-CoV-2 infection through the ' 'chemical production of nitric oxide (NO). NO is a gaseous free radical that is largely ' 'produced by the enzyme NO synthase (NOS) in cells. NO produced by upper epidermal cells ' 'contributes to the inactivation of viruses and bacteria contained in air or aerosols. In ' 'addition to enzymatic production, NO can be generated by the chemical reduction of inorganic ' 'nitrite (NO2−), an alternative mechanism for NO production in living organisms. Dietary ' 'vitamin C, largely contained in fruits and vegetables, can reduce the nitrite in saliva to ' 'produce NO in the oral cavity when chewing foods. In the stomach, salivary nitrite can also ' 'be reduced to NO by vitamin C secreted from the epidermal cells of the stomach. The strong ' 'acidic pH of gastric juice facilitates the chemical reduction of salivary nitrite to produce ' 'NO. Vitamin C contributes in multiple ways to the host innate immune system as a first-line ' 'defense mechanism against pathogens. Highlighting chemical NO production by vitamin C, we ' 'suggest that controversies on the therapeutic effects of vitamin C in previous clinical ' 'trials may partly be due to less appreciation of the pleiotropic functions of vitamin C as a ' 'universal bioreductant.</jats:p>', 'DOI': '10.3390/microorganisms11020397', 'type': 'journal-article', 'created': {'date-parts': [[2023, 2, 6]], 'date-time': '2023-02-06T09:08:07Z', 'timestamp': 1675674487000}, 'page': '397', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Pleiotropic Functions of Nitric Oxide Produced by Ascorbate for the Prevention and Mitigation of ' 'COVID-19: A Revaluation of Pauling’s Vitamin C Therapy', 'prefix': '10.3390', 'volume': '11', 'author': [ { 'given': 'Hideo', 'family': 'Yamasaki', 'sequence': 'first', 'affiliation': [ { 'name': 'Faculty of Science, University of the Ryukyus, Nishihara ' '903-0213, Okinawa, Japan'}]}, { 'ORCID': 'http://orcid.org/0000-0002-3793-1146', 'authenticated-orcid': False, 'given': 'Hideyuki', 'family': 'Imai', 'sequence': 'additional', 'affiliation': [ { 'name': 'Faculty of Science, University of the Ryukyus, Nishihara ' '903-0213, Okinawa, Japan'}]}, { 'ORCID': 'http://orcid.org/0000-0002-8277-1188', 'authenticated-orcid': False, 'given': 'Atsuko', 'family': 'Tanaka', 'sequence': 'additional', 'affiliation': [ { 'name': 'Faculty of Science, University of the Ryukyus, Nishihara ' '903-0213, Okinawa, Japan'}]}, { 'ORCID': 'http://orcid.org/0000-0003-3425-7085', 'authenticated-orcid': False, 'given': 'Joji M.', 'family': 'Otaki', 'sequence': 'additional', 'affiliation': [ { 'name': 'Faculty of Science, University of the Ryukyus, Nishihara ' '903-0213, Okinawa, Japan'}]}], 'member': '1968', 'published-online': {'date-parts': [[2023, 2, 3]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'first-page': '425', 'DOI': '10.1016/j.jmii.2020.04.015', 'article-title': 'ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, ' 'multi-organ failure, and COVID-19 disease outcome', 'volume': '53', 'author': 'Devaux', 'year': '2020', 'journal-title': 'J. 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