Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1175175 (SARS)
 19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major risk factors to fatal outcome in COVID-19 patients, i.e., elderliness and pre-existing metabolic and cardiovascular diseases (CVD), share in common the characteristic of being chronic degenerative diseases of inflammatory nature associated with defective heat shock response (HSR). The molecular components of the HSR, the principal metabolic pathway leading to the physiological resolution of inflammation, is an anti-inflammatory biochemical pathway that involves molecular chaperones of the heat shock protein (HSP) family during homeostasis-threatening stressful situations (e.g., thermal, oxidative and metabolic stresses). The entry of SARS coronaviruses in target cells, on the other hand, aggravates the already-jeopardized HSR of this specific group of patients. In addition, cellular counterattack against virus involves interferon (IFN)-mediated inflammatory responses. Therefore, individuals with impaired HSR cannot resolve virus-induced inflammatory burst physiologically, being susceptible to exacerbated forms of inflammation, which leads to a fatal "cytokine storm". Interestingly, some species of bats that are natural reservoirs of zoonotic viruses, including SARS-CoV-2, possess an IFN-based antiviral inflammatory response perpetually activated but do not show any sign of disease or cytokine storm. This is possible because bats present a constitutive HSR that is by far (hundreds of times) more intense and rapid than that of human, being associated with a high core temperature. Similarly in humans, fever is a physiological inducer of HSR while antipyretics, which block the initial phase of inflammation, impair the resolution phase of inflammation through the HSR. These findings offer a rationale for the reevaluation of patient care and fever reduction in SARS, including COVID-19.
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PMID:Suppressed anti-inflammatory heat shock response in high-risk COVID-19 patients: lessons from basic research (inclusive bats), light on conceivable therapies. 3274 72

The 60-kDa heat shock protein (HSP60) is a chaperone essential for mitochondrial proteostasis ensuring thus sufficient aerobic energy production. In pathological conditions, HSP60 can be translocated from the mitochondria and excreted from the cell. In turn, the extracellular HSP60 has a strong ability to trigger and enhance inflammatory response with marked proinflammatory cytokine induction, which is mainly mediated by Toll-like receptor binding. Previous studies have found increased circulating levels of HSP60 in hypertensive patients, as well as enhanced HSP60 expression and membrane translocation in the hypertrophic myocardium. These observations are of particular interest, since they could provide a possible pathophysiological explanation of the severe course and worse outcome of severe acute respiratory syndrome coronavirus 2 infection in hypertensive patients, repeatedly reported during the recent coronavirus disease 2019 (COVID-19) pandemic and related to hyperinflammatory response and cytokine storm development during the third phase of the disease. In this regard, pharmacological inhibition of HSP60 could attract attention to potentially ameliorate inappropriate inflammatory reaction in severe COVID-19 patients. Among HSP60 antagonizing drugs, mizoribine is the most intriguing, since it is clinically approved and exerts antiviral activity. However, this topic requires to be further scrutinized.
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PMID:COVID-19 and hypertension: is the HSP60 culprit for the severe course and worse outcome? 3288 2