Yamasaki Hideo, Imai Hideyuki, Tanaka Atsuko, Otaki Joji M
Faculty of Science, University of the Ryukyus, Nishihara 903-0213, Okinawa, Japan.
Microorganisms. 2023 Feb 3;11(2):397. doi: 10.3390/microorganisms11020397.
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 (NO), 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.
莱纳斯·鲍林曾荣获诺贝尔化学奖，他提出大剂量的维生素C（L-抗坏血酸）可能对普通感冒起到预防或治疗作用。维生素C疗法曾在临床试验中进行测试，但当时并未找到确凿证据。尽管鲍林的提议长期以来遭到强烈批评，但维生素C疗法仍在继续作为包括2019冠状病毒病（COVID-19）在内的多种疾病的治疗方法进行测试。COVID-19的病原体严重急性呼吸综合征冠状病毒2（SARS-CoV-2）属于β冠状病毒谱系，该谱系包括人类冠状病毒、严重急性呼吸综合征（SARS）和中东呼吸综合征（MERS）。本综述旨在揭示维生素C的抗病毒活性，其可能通过一氧化氮（NO）的化学生成来预防SARS-CoV-2感染。NO是一种气态自由基，主要由细胞中的一氧化氮合酶（NOS）产生。上层表皮细胞产生的NO有助于使空气或气溶胶中所含的病毒和细菌失活。除了酶促生成外，NO还可通过无机亚硝酸盐（NO₂⁻）的化学还原产生，这是生物体中NO生成的另一种机制。大量存在于水果和蔬菜中的膳食维生素C在咀嚼食物时可将唾液中的亚硝酸盐还原，从而在口腔中产生NO。在胃中，唾液亚硝酸盐也可被胃表皮细胞分泌的维生素C还原为NO。胃液的强酸性pH值有助于唾液亚硝酸盐的化学还原以产生NO。维生素C作为抵御病原体的一线防御机制，以多种方式对宿主先天免疫系统发挥作用。强调维生素C产生化学NO的作用，我们认为先前临床试验中关于维生素C治疗效果的争议可能部分是由于对维生素C作为一种通用生物还原剂的多效性功能认识不足。
