Renin-angiotensin system: The unexpected flaw inside the human immune system revealed by SARS-CoV-2

Roncati, Luca; Gallo, Graziana; Manenti, Antonio; Palmieri, Beniamino

doi:10.1016/j.mehy.2020.109686

Cited by 35 publications

(32 citation statements)

References 4 publications

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“…In the past years, pulmonary megakaryocytes were immunohistochemically quantified on 30 consecutive hospital necropsies and their concentration was noticed to increase during lung infections [6,7]. In this regard, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the current pandemic named coronavirus disease 2019 (COVID-19), is able to infect type II pneumocytes via angiotensin-converting enzyme 2 [8]. The virus-induced damage to these cells appointed to pulmonary surfactant production causes its deficiency with subsequent formation of hyaline membranes, which line or fill the alveoli as wax blocking gas exchanges and resulting in hypoxemia plus hypercapnia [9].…”

Section: Introductionmentioning

confidence: 99%

A proof of evidence supporting abnormal immunothrombosis in severe COVID-19: naked megakaryocyte nuclei increase in the bone marrow and lungs of critically ill patients

Roncati

Ligabue

Nasillo³

et al. 2020

Platelets

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Coronavirus disease 2019 (COVID-19) is a global public health emergency with many clinical facets, and new knowledge about its pathogenetic mechanisms is deemed necessary; among these, there are certainly coagulation disorders. In the history of medicine, autopsies and tissue sampling have played a fundamental role in order to understand the pathogenesis of emerging diseases, including infectious ones; compared to the past, histopathology can be now expanded by innovative techniques and modern technologies. For the first time in worldwide literature, we provide a detailed postmortem and biopsy report on the marked increase, up to 1 order of magnitude, of naked megakaryocyte nuclei in the bone marrow and lungs from serious COVID-19 patients. Most likely related to high interleukin-6 serum levels stimulating megakaryocytopoiesis, this phenomenon concurs to explain well the pulmonary abnormal immunothrombosis in these critically ill patients, all without molecular or electron microscopy signs of megakaryocyte infection.

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Section: Introductionmentioning

confidence: 99%

A proof of evidence supporting abnormal immunothrombosis in severe COVID-19: naked megakaryocyte nuclei increase in the bone marrow and lungs of critically ill patients

Roncati

Ligabue

Nasillo³

et al. 2020

Platelets

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“…Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency around the world and the acquisition of new knowledge about its immunopathogenesis is required in the attempt to reduce the death burden, globally. As well known, naїve T-helper cells (T h 0) can detect pathogens never encountered before, like the specific case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent responsible for the disease, able to infect the human cells via angiotensin-converting enzyme 2 receptors [1]. Classically, on the basis of the novel infectious agent, T h 0 polarize the immune response into type 1 T-helper (T h 1), the default response in immunocompetent subjects to intracellular or phagocytosable pathogens (e.g.…”

mentioning

confidence: 99%

Type 3 hypersensitivity in COVID-19 vasculitis

Roncati

Ligabue

Fabbiani

et al. 2020

Clinical Immunology

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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“…It was observed that ACE2 receptor targets are those which have been used in treatments for diabetics, heart disease etc. 23,24 Additionally, ACE2 receptors are present in intestine, kidney, oral mucosa and heart endothelium. 21,24 Eventually, overexpression of ACE receptors result due to administration of ACE inhibitors as reported in rat model experiments.…”

Section: Methodsologymentioning

confidence: 99%

“…receptors. 23 This might be the most valid reason why diabetic and heart patients are at larger risk for SARS-Cov-2. 27 Thus, it is the most urgent need to develop a safer and effective therapy.…”

Section: Methodsologymentioning

confidence: 99%

Protease Inhibitors: Strategy to Disrupt COVID 19 Contagion

Paul

Bhattacharjee

Sarma

2020

Preprint

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Background: The COVID 2019 (Corona Virus Disease) has been currently going pandemic as per WHO (World Health Organisation) situation reports. The major differentiating point in this virus is the presence of a unique furin cleavage site. Our insilico study points out to the effectiveness of a potent plant origin furin inhibitor. We exploited the aspect of the cleavage machinery of furin which is critical and indispensible for the entry of SARS-CoV-2 (Severe Acute Respiratory Syndrome –Corona Virus 2) in human cells and subsequent massive contagion. Most of the drugs are presently targeting ACEII (Angiotensin Converting Enzyme 2) receptor. But these options have injurious effects in diabetics and cardiac patients. Repurposing of old drugs are the current undergoing therapeutic measures as per the EUA (Emergency Usage Administration) of Food and Drug Administration. These aspects could be avoided if we develop a better and safer strategized drug . Methods In silico analysis of plant based protein analogs to inhibit furin protein. Results Significant interactions of proposed analogs of protease inhibitor of plant origin against furin protein. Furin inhibitors would be incredible drug targets against cancers, MERS CoV (Middle East Respiratory Syndrome) and most urgently SARS- CoV-2. Conclusion We report the first of its kind of furin inhibitor and believe that this major finding would fast track arenas for drug trials.

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Renin-angiotensin system: The unexpected flaw inside the human immune system revealed by SARS-CoV-2

Cited by 35 publications

References 4 publications

A proof of evidence supporting abnormal immunothrombosis in severe COVID-19: naked megakaryocyte nuclei increase in the bone marrow and lungs of critically ill patients

A proof of evidence supporting abnormal immunothrombosis in severe COVID-19: naked megakaryocyte nuclei increase in the bone marrow and lungs of critically ill patients

Type 3 hypersensitivity in COVID-19 vasculitis

Protease Inhibitors: Strategy to Disrupt COVID 19 Contagion

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