Whole Systems Research Institute, 1020 SW Taylor St Ste. 340, Portland, OR 97239, United States.
Whole Systems Research Institute, 1020 SW Taylor St Ste. 340, Portland, OR 97239, United States.
Med Hypotheses. 2020 Oct;143:109862. doi: 10.1016/j.mehy.2020.109862. Epub 2020 May 30.
COVID-19, a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread across the globe. Predisposing factors such as age, diabetes, cardiovascular disease, and lowered immune function increase the risk of disease severity. T cell exhaustion, high viral load, and high levels of TNF-ɑ, IL1β, IL6, IL10 have been associated with severe SARS-CoV-2. Cytokine and antigen overstimulation are potentially responsible for poor humoral response to the virus. Lower cellular redox status, which leads to pro-inflammatory states mediated by TNF-ɑ is also potentially implicated. In vivo, in vitro, and human clinical trials have demonstrated N-acetylcysteine (NAC) as an effective method of improving redox status, especially when under oxidative stress. In human clinical trials, NAC has been used to replenish glutathione stores and increase the proliferative response of T cells. NAC has also been shown to inhibit the NLRP3 inflammasome pathway (IL1β and IL18) in vitro, and decrease plasma TNF-ɑ in human clinical trials. Mediation of the viral load could occur through NAC's ability to increase cellular redox status via maximizing the rate limiting step of glutathione synthesis, and thereby potentially decreasing the effects of virally induced oxidative stress and cell death. We hypothesize that NAC could act as a potential therapeutic agent in the treatment of COVID-19 through a variety of potential mechanisms, including increasing glutathione, improving T cell response, and modulating inflammation. In this article, we present evidence to support the use of NAC as a potential therapeutic agent in the treatment of COVID-19.
COVID-19，一种由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的呼吸道疾病，继续在全球范围内传播。年龄、糖尿病、心血管疾病和免疫功能下降等易感因素会增加疾病严重程度的风险。T 细胞耗竭、高病毒载量和 TNF-ɑ、IL1β、IL6、IL10 水平升高与严重的 SARS-CoV-2 有关。细胞因子和抗原过度刺激可能是导致对病毒产生不良体液反应的原因。细胞内氧化还原状态较低，导致 TNF-ɑ介导的促炎状态，也可能与此有关。在体内、体外和人体临床试验中，N-乙酰半胱氨酸（NAC）已被证明是改善氧化还原状态的有效方法，尤其是在氧化应激下。在人体临床试验中，NAC 已被用于补充谷胱甘肽储存并增加 T 细胞的增殖反应。NAC 还被证明可以抑制体外 NLRP3 炎症小体途径（IL1β 和 IL18），并降低人体临床试验中的血浆 TNF-ɑ。NAC 可以通过增加细胞内氧化还原状态来调节病毒载量，其作用机制可能是通过最大化谷胱甘肽合成的限速步骤，从而潜在地减少病毒诱导的氧化应激和细胞死亡的影响。我们假设 NAC 通过多种潜在机制，包括增加谷胱甘肽、改善 T 细胞反应和调节炎症，可作为 COVID-19 治疗的潜在治疗剂。在本文中，我们提供了支持 NAC 作为 COVID-19 治疗潜在治疗剂的证据。
