sars - cov -2诱导的宿主代谢重编程(HMR):营养干预对COVID-19和COVID-19急性后后遗症(PASC)的全球管理

A. Naidu, F. Shahidi, Chin-Kun Wang, Kenji Sato, A. Wirakartakusumah, Ogugua C. Aworhf, B. Halliwell, Roger A. Clemensh
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引用次数: 3

摘要

“严重急性呼吸综合征冠状病毒2”(SARS-CoV-2)是一种高度传染性的病毒性病原体,是正在进行的“2019冠状病毒病”(COVID-19)大流行的罪魁祸首。目前针对SARS-CoV-2的重新用途的抗病毒干预措施分为两大类:第一类代表药物家族,主要是直接针对该病毒的疫苗,第二类包括一类干扰宿主细胞机制的特定抑制剂,这对病毒感染和复制至关重要。通过疫苗和改头换面的治疗方法控制COVID-19大流行的全球努力只是阶段性的胜利。几种令人关注的SARS-CoV-2变体(VOCs)的出现已经危及了几种疫苗接种和药物治疗方案,这凸显了针对高度保守结构域的特定抗病毒干预措施的迫切必要性,这些结构域在SARS-CoV-2基因组中不太可能发生突变。一些阻断病毒酶的生物活性植物化学物质,如nsp5/主蛋白酶(Mpro)和rna依赖的nsp7/nsp8/nsp12 rna依赖的rna -聚合酶(RdRp)复合物,在这方面得到了广泛的研究。SARS-CoV-2感染引发复杂的人类宿主-病原体相互作用,导致“宿主代谢重编程”(HMR)、铁(Fe)-氧化还原失调(FeRD)和线粒体功能改变,从而累积破坏涉及细胞能量和抗氧化酶功能的几种代谢途径;从而破坏宿主的先天防御。循环/RAAS轴与FeRD有关,铁氧化还原稳态(Fe-R-H)的任何改变或失衡都可能导致“新发”代谢紊乱(即糖尿病)。COVID-19急性后后遗症中这种固有的身体损伤及其长期健康后果需要有效的营养干预策略,特别是在器官系统功能和免疫系统动力学的界面。PASC的长期后遗症表明,由于抗原刺激时间延长(也由于疫苗暴露),COVID-19患者的免疫衰竭速度加快。异常的免疫代谢也可能导致全身性紊乱(即FeRD)、ROS/RNS产生、氧化应激和亚硝化应激,这可能引发多器官疾病,从轻微症状到丧失行为能力状态,并在COVID-19康复后持续数周或更长时间的生活质量下降。PASC的五个最长期的临床表现包括疲劳、头痛、注意力障碍、脱发和呼吸困难。这篇叙述性综述阐明了与COVID-19幸存者的八个主要生理系统(即肺、神经认知、心血管、肾脏、胃肠/肝胆、内分泌、骨骼肌和生殖)相关的复杂损伤和后遗症,这些生理系统由FeRD触发,由HMR放大,线粒体功能和ACE2/RAAS轴发生改变。我们试图解释COVID-19幸存者中残留的非病毒性宿主代谢紊乱和并发症的持续流行,以及特定宿主系统靶向营养干预措施(如天然植物抗炎药、免疫调节剂、抗氧化剂和宏/微量营养素代谢优化剂)对新出现的COVID-19后代谢综合征PASC的支持作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SARS-CoV-2-induced Host Metabolic Reprogram (HMR): Nutritional Interventions for Global Management of COVID-19 and Post-Acute Sequelae of COVID-19 (PASC)
‘Severe acute respiratory syndrome coronavirus 2’ (SARS-CoV-2) is a highly transmissible viral pathogen responsible for the ongoing ‘coronavirus disease 2019’ (COVID-19) pandemic.  The current re-purposed antiviral interventions against SARS-CoV-2 are classified into two major groups: Group-1 represents the family of drugs, mainly the vaccines that directly target the virus, and Group-2 includes a specific class of inhibitors that interfere with the host-cell machinery, which is critical for viral infection and replication.  Global efforts to control COVID-19 pandemic with vaccines and repurposed therapeutics represent only a phased victory.  The emergence of several SARS-CoV-2 variants of concern (VOCs) has compromised several vaccinations and pharma-therapeutic protocols, which highlights the dire necessity for specific antiviral interventions that target highly conserved domains, which are less likely to mutate in the SARS-CoV-2 genome.  Several bioactive phytochemicals that block viral enzymes such as nsp5/main proteinase (Mpro) and RNA-dependent nsp7/nsp8/nsp12 RNA-dependent RNA-polymerase (RdRp) complex, are extensively investigated in this direction.  The SARS-CoV-2 infection triggers a complex human host-pathogen interaction(s) resulting in ‘host metabolic reprogramming’ (HMR), iron (Fe)-redox dysregulation (FeRD), and altered mitochondrial function that cumulatively disrupt several metabolic pathways involved in cellular energy and antioxidant enzyme function; thereby, compromise the innate host defense.  The circulatory/RAAS axis contributes to FeRD and any alteration or imbalance in the Fe-redox homeostasis (Fe-R-H) may lead to ‘new onset’ metabolic disorders (i.e., diabetes).  Such inherent body damage and its long-term health consequences in post-acute sequelae of COVID-19 (PASC) require effective nutritional intervention strategies, particularly at the interface of organ system functions and immune system dynamics.  The long-term sequelae of PASC indicate an accelerated rate of immune exhaustion in COVID-19 patients, due to prolonged antigen stimulation (also due to vaccine exposure).  Abnormal immune metabolism may also cause systemic perturbations (i.e., FeRD), ROS/RNS production, oxidative and nitrosative stress, which could trigger multi-organ disorders ranging from mild symptoms to an incapacitating state and reduced quality of life that could last for weeks or longer following recovery from COVID-19.  The five most long-term clinical manifestations of PASC include fatigue, headache, attention disorder, hair loss, and dyspnea.  This narrative review elucidates the intricate impairments and sequelae associated with eight major physiological systems in COVID-19 survivors (i.e., pulmonary, neuro-cognitive, cardiovascular, renal, gastrointestinal/hepato-biliary, endocrinal, skeleton-muscular, and reproductive) – triggered by the FeRD, amplified by the HMR, altered mitochondrial function and ACE2/RAAS axis.  We have attempted to explain the ongoing epidemic of the residual, non-viral host metabolic disorders and complications in COVID-19 survivors and the supportive role of specific host system-targeted nutritional interventions such as natural plant-based anti-inflammatories, immune-modulators, antioxidants, and macro-/micronutrient metabolic optimizers to manage PASC, the newly emerged post-COVID metabolic syndrome.
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