Nasi Aikaterini, McArdle Stephanie, Gaudernack Gustav, Westman Gabriel, Melief Cornelis, Rockberg Johan, Arens Ramon, Kouretas Demetrios, Sjölin Jan, Mangsbo Sara
Ultimovacs AB, Uppsala Sweden.
Dept Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Toxicol Rep. 2020 Jun 18;7:768-771. doi: 10.1016/j.toxrep.2020.06.003. eCollection 2020.
During the current COVID-19 pandemic, a need for evaluation of already available drugs for treatment of the disease is crucial. Hereby, based on literature review from the current pandemic and previous outbreaks with corona viruses we analyze the impact of the virus infection on cell stress responses and redox balance. High levels of mortality are noticed in elderly individuals infected with SARS-CoV2 and during the previous SARS-CoV1 outbreak. Elderly individuals maintain a chronic low level of inflammation which is associated with oxidative stress and inflammatory cytokine production, a condition that increases the severity of viral infections in this population. Coronavirus infections can lead to alterations of redox balance in infected cells through modulation of NAD + biosynthesis, PARP function along with altering proteasome and mitochondrial function in the cell thereby leading to enhanced cell stress responses which further exacerbate inflammation. ROS production can increase IL-6 production and lipid peroxidation resulting in cell damage. Therefore, early treatment with anti-oxidants such as NAC during COVID-19 can be a way to bypass the excessive inflammation and cell damage that lead to severe infection, thus early NAC as intervention should be evaluated in a clinical trial setting.
在当前的新冠疫情期间,评估已有的治疗该疾病的药物至关重要。在此,基于对当前疫情以及既往冠状病毒爆发的文献综述,我们分析了病毒感染对细胞应激反应和氧化还原平衡的影响。在感染新冠病毒的老年人以及既往非典冠状病毒-1爆发期间,均发现了高死亡率。老年人维持着慢性低水平炎症状态,这与氧化应激和炎性细胞因子产生相关,这种状况会增加该人群中病毒感染的严重程度。冠状病毒感染可通过调节NAD+生物合成、PARP功能以及改变细胞中的蛋白酶体和线粒体功能,导致受感染细胞氧化还原平衡的改变,从而引发增强的细胞应激反应,进而加剧炎症。活性氧的产生可增加白细胞介素-6的产生和脂质过氧化,导致细胞损伤。因此,在新冠疫情期间早期使用抗氧化剂如N-乙酰半胱氨酸进行治疗,可能是一种避免导致严重感染的过度炎症和细胞损伤的方法,因此应在临床试验环境中评估早期使用N-乙酰半胱氨酸作为干预措施的效果。