Targeting Neprilysin (NEP) pathways: A potential new hope to defeat COVID-19 ghost

Tabaa, Manar Mohammed El; Tabaa, Maram Mohammed El

doi:10.1016/j.bcp.2020.114057

Cited by 33 publications

(34 citation statements)

References 270 publications

(306 reference statements)

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“…22 Interestingly, bradykinin1-9 can also be inactivated by neprilysin (CD10), which is an important activation and differentiation marker expressed by neutrophils, possibly linking neutrophils with bradykinin-induced pulmonary edema. 23,24 The increase in expression of activation markers on neutrophils is generally used to study the role of neutrophils in vivo in health and disease. [25][26][27] However, these cells are notoriously sensitive to ex vivo manipulation and it is therefore essential to minimally manipulate the cells ex vivo.…”

Section: Introductionmentioning

confidence: 99%

Flow cytometric evaluation of the neutrophil compartment in COVID-19 at hospital presentation: A normal response to an abnormal situation

Spijkerman

Bongers

Bindels

et al. 2020

Journal of Leukocyte Biology

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Coronavirus disease 2019 (COVID‐19) is a rapidly emerging pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Critical COVID‐19 is thought to be associated with a hyper‐inflammatory process that can develop into acute respiratory distress syndrome, a critical disease normally mediated by dysfunctional neutrophils. This study tested the hypothesis whether the neutrophil compartment displays characteristics of hyperinflammation in COVID‐19 patients. Therefore, a prospective study was performed on all patients with suspected COVID‐19 presenting at the emergency room of a large academic hospital. Blood drawn within 2 d after hospital presentation was analyzed by point‐of‐care automated flow cytometry and compared with blood samples collected at later time points. COVID‐19 patients did not exhibit neutrophilia or eosinopenia. Unexpectedly neutrophil activation markers (CD11b, CD16, CD10, and CD62L) did not differ between COVID‐19‐positive patients and COVID‐19‐negative patients diagnosed with other bacterial/viral infections, or between COVID‐19 severity groups. In all patients, a decrease was found in the neutrophil maturation markers indicating an inflammation‐induced left shift of the neutrophil compartment. In COVID‐19 this was associated with disease severity.

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Section: Introductionmentioning

confidence: 99%

Flow cytometric evaluation of the neutrophil compartment in COVID-19 at hospital presentation: A normal response to an abnormal situation

Spijkerman

Bongers

Bindels

et al. 2020

Journal of Leukocyte Biology

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“…As previously mentioned, SARS-CoV-2 enters the CNS via the ACE2 or TMPRSS2 receptors ( El Tabaa and El Tabaa, 2020 ; Nemoto et al, 2020 ). In order to decline SARS-CoV-2 entry to neural cells, ACE2 activity should be declined ( Battagello et al, 2020 ).…”

Section: Potential Of Phytochemicals Against Covid-19 Neurological Asmentioning

confidence: 98%

“…It has been shown that SARS-CoV-2 mainly enters the CNS via the ACE2 or TMPRSS2 receptors. These receptors are expressed in the glial cells of brain/spinal cord and thereby facilitates the invasion of coronavirus to the spinal cord, which is essential for the host cell entry of SARS-CoV-2 and also plasma membrane fusion ( El Tabaa and El Tabaa, 2020 ; Nemoto et al, 2020 ). Also, it has been indicated that when coronavirus enters the cells, ACE2 will break and shed by ADAM Metallopeptidase Domain 17 (ADAM17) into the membrane space ( Li and De Clercq, 2020 ).…”

Section: Role Of Renin-angiotensin System In the Neuronal Manifestatimentioning

confidence: 99%

“…Recent reports indicated that Ang II act via two G protein-coupled receptors (GPCR) such as AT1R, angiotensin type-2 receptor (AT2R) which expressed in human lung tissue. Besides, the activations of Ang II can be mediated by AT1R through enhancing several signaling pathways such as MAPK/ERK, IP3/diacylglycerol, tyrosine kinases, and NF-κB ( Balakumar and Jagadeesh, 2014 ; El Tabaa and El Tabaa, 2020 ). In a parallel way, AT1 stimulates monocytes, macrophages and vascular smooth muscle cells to generate TNF-α and IL-6 ( Balakumar and Jagadeesh, 2014 ).…”

Section: Role Of Renin-angiotensin System In the Neuronal Manifestatimentioning

confidence: 99%

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Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach

et al. 2021

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The novel coronavirus 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a wide range of manifestations. In this regard, growing evidence is focusing on COVID-19 neurological associations; however, there is a lack of established pathophysiological mechanisms and related treatments. Accordingly, a comprehensive review was conducted, using electronic databases, including PubMed, Scopus, Web of Science, and Cochrane, along with the author’s expertize in COVID-19 associated neuronal signaling pathways. Besides, potential phytochemicals have been provided against neurological signs of COVID-19. Considering a high homology among SARS-CoV, Middle East Respiratory Syndrome and SARS-CoV-2, revealing their precise pathophysiological mechanisms seems to pave the road for the treatment of COVID-19 neural manifestations. There is a complex pathophysiological mechanism behind central manifestations of COVID-19, including pain, hypo/anosmia, delirium, impaired consciousness, pyramidal signs, and ischemic stroke. Among those dysregulated neuronal mechanisms, neuroinflammation, angiotensin-converting enzyme 2 (ACE2)/spike proteins, RNA-dependent RNA polymerase and protease are of special attention. So, employing multi-target therapeutic agents with considerable safety and efficacy seems to show a bright future in fighting COVID-19 neurological manifestations. Nowadays, natural secondary metabolites are highlighted as potential multi-target phytochemicals in combating several complications of COVID-19. In this review, central pathophysiological mechanisms and therapeutic targets of SARS-CoV-2 has been provided. Besides, in terms of pharmacological mechanisms, phytochemicals have been introduced as potential multi-target agents in combating COVID-19 central nervous system complications.

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“…With the support of our esteemed professor, we presented a multi-country survey of COVID-19 to characterize mortality-associated factors in elderly males with comorbidities [111] . In addition to remdesivir and dexamethasone, many strategies are still under development to treat COVID-19 [113] , [114] , [115] , [116] , [117] , [118] , [119] , [120] , [121] , [122] , [123] , [124] , [125] , [126] , [127] .…”

Section: The Life-long Passion For Teaching and Researchmentioning

confidence: 99%

Life-long passion for antiviral research and drug development: 80th birthday of Prof. Dr. Erik De Clercq

Yue

et al. 2021

Biochemical Pharmacology

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Targeting Neprilysin (NEP) pathways: A potential new hope to defeat COVID-19 ghost

Cited by 33 publications

References 270 publications

Flow cytometric evaluation of the neutrophil compartment in COVID-19 at hospital presentation: A normal response to an abnormal situation

Flow cytometric evaluation of the neutrophil compartment in COVID-19 at hospital presentation: A normal response to an abnormal situation

Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach

Life-long passion for antiviral research and drug development: 80th birthday of Prof. Dr. Erik De Clercq

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