SARS-CoV-2 virus, the etiologic agent of COVID-19, has affected almost every aspect of human life, precipitating stress-related pathology in vulnerable individuals. As the prevalence rate of posttraumatic stress disorder in pandemic survivors exceeds that of the general and special populations, the virus may predispose to this disorder by directly interfering with the stress-processing pathways. The SARS-CoV-2 interactome has identified several antigens that may disrupt the blood-brain-barrier by inducing premature senescence in many cell types, including the cerebral endothelial cells. This enables the stress molecules, including angiotensin II, endothelin-1 and plasminogen activator inhibitor 1, to aberrantly activate the amygdala, hippocampus, and medial prefrontal cortex, increasing the vulnerability to stress related disorders. This is supported by observing the beneficial effects of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in both posttraumatic stress disorder and SARS-CoV-2 critical illness. In this narrative review, we take a closer look at the virus-host dialog and its impact on the renin-angiotensin system, mitochondrial fitness, and brain-derived neurotrophic factor. We discuss the role of furin cleaving site, the fibrinolytic system, and Sigma-1 receptor in the pathogenesis of psychological trauma. In other words, learning from the virus, clarify the molecular underpinnings of stress related disorders, and design better therapies for these conditions. In this context, we emphasize new potential treatments, including furin and bromodomains inhibitors. Graphical Abstract 1 Covid-19 triggers endothelial cell (EC) senescence and dysfunction, likely predisposing to PTSD by increasing microvascular permeability that enables the extravasation of stress molecules into the brain trauma-processing networks in amygdala, hippocampus and the medial prefrontal cortex. The virus upregulates host angiotensin II (ANG II) (via S1 antigen), usurps furin/plasmin (via S2 antigen), mitochondria (via ORF9b), and Sigma-1 receptors (Sig-1Rs) via NSP6. These structures, previously associated with PTSD, link the SARS-CoV-2 virus to increased susceptibility for stress related disorders. As ECs are major producers of brain derived neurotrophic factor (BDNF), a neurotrophin altered in PTSD, senescent ECs lower this molecule further, predisposing to stress related disorders.
【저자키워드】 COVID-19, SARS-CoV-2, Mitochondria, PTSD, endothelia, Lactate, 【초록키워드】 pathology, pandemic, therapy, Pathogenesis, Stress, furin, susceptibility, SARS-CoV-2 virus, virus, inhibitors, Brain, Antigen, renin-angiotensin system, Prevalence, endothelial cells, Premature, Psychological, Orf9b, receptor, molecular, inhibitor, Critical, trauma, Endothelial cell, angiotensin receptor blocker, NSP6, Pathways, structures, Trigger, mitochondrial, cell types, dysfunction, Posttraumatic Stress, BDNF, fibrinolytic system, disorders, enzyme, potential treatments, microvascular permeability, disorder, survivor, S2 antigen, Host, Effect, populations, affected, supported, activate, individuals, senescent, conditions, disrupt, ANG, cleaving, the SARS-CoV-2 virus, upregulate, 【제목키워드】 insight,