S.T. Bio-Life, San Antonio, TX 78240, USA.
Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, 37073 Göttingen, Germany.
Molecules. 2020 Sep 25;25(19):4410. doi: 10.3390/molecules25194410.
Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen's spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution. Practically, it has a broader protective spectrum than that of only targeting the specific pathogens, which differ in terms of susceptibility. Methods for host targeting applied in one pandemic can even be effective for upcoming pandemics with different pathogens. This is even more urgent if we consider the possible concomitance of two respiratory diseases with potential multi-organ afflictions such as Coronavirus disease 2019 (COVID-19) and seasonal flu. Melatonin is a molecule that can enhance the host's tolerance against pathogen invasions. Due to its antioxidant, anti-inflammatory, and immunoregulatory activities, melatonin has the capacity to reduce the severity and mortality of deadly virus infections including COVID-19. Melatonin is synthesized and functions in mitochondria, which play a critical role in viral infections. Not surprisingly, melatonin synthesis can become a target of viral strategies that manipulate the mitochondrial status. For example, a viral infection can switch energy metabolism from respiration to widely anaerobic glycolysis even if plenty of oxygen is available (the Warburg effect) when the host cell cannot generate acetyl-coenzyme A, a metabolite required for melatonin biosynthesis. Under some conditions, including aging, gender, predisposed health conditions, already compromised mitochondria, when exposed to further viral challenges, lose their capacity for producing sufficient amounts of melatonin. This leads to a reduced support of mitochondrial functions and makes these individuals more vulnerable to infectious diseases. Thus, the maintenance of mitochondrial function by melatonin supplementation can be expected to generate beneficial effects on the outcome of viral infectious diseases, particularly COVID-19.
防治传染病，尤其是病毒性传染病，是维护人类健康的艰巨任务。针对病原体或宿主是不同的策略，但目的相同，即遏制病原体的传播和治愈疾病。针对宿主以提高对病原体的耐受性似乎具有很大的优势，并且是进化中使用的一种策略。实际上，与仅针对特定病原体相比，它具有更广泛的保护谱，而针对特定病原体的策略在易感性方面有所不同。在一种大流行中应用的宿主靶向方法甚至可能对具有不同病原体的未来大流行有效。如果考虑到可能同时发生两种具有潜在多器官损伤的呼吸道疾病，如 2019 年冠状病毒病（COVID-19）和季节性流感，情况就更加紧迫了。褪黑素是一种可以增强宿主对病原体入侵的耐受性的分子。由于其抗氧化、抗炎和免疫调节作用，褪黑素具有减轻包括 COVID-19 在内的致命病毒感染的严重程度和死亡率的能力。褪黑素在线粒体中合成并发挥作用，线粒体在病毒感染中起着关键作用。毫不奇怪，褪黑素的合成可能成为病毒策略的目标，这些策略操纵线粒体状态。例如，当宿主细胞不能产生乙酰辅酶 A 时，病毒感染可以将能量代谢从呼吸切换到广泛的无氧糖酵解，即使有大量氧气可用（Warburg 效应），而乙酰辅酶 A 是褪黑素生物合成所需的代谢物。在某些条件下，包括衰老、性别、预先存在的健康状况、已经受损的线粒体，当暴露于进一步的病毒挑战时，它们丧失产生足够量褪黑素的能力。这导致线粒体功能的支持减少，使这些个体更容易受到传染病的影响。因此，通过褪黑素补充维持线粒体功能有望对病毒感染性疾病，特别是 COVID-19 的结果产生有益影响。
