Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury

Öz, Murat; Lorke, Dietrich

doi:10.1016/j.biopha.2020.111193

Cited by 46 publications

(49 citation statements)

References 359 publications

(379 reference statements)

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“…The basis for the hypothesis that the virus may be detected in such cases is that the angiotensin-converting enzyme 2 (ACE2) binding affinity of the S protein is an important determinant of SARS-CoV-2 infectivity and disease severity. 28 Studies have shown the predominance of these receptors in the lower respiratory tract and SARS CoV-2 having higher receptor tropism in the lower respiratory tract. 16,28 Although studies have a wide range of positivity, a pooled estimate of 11% suggests that BAL may be used to confirm SARS CoV-2 infection where nasopharyngeal specimens are negative, and there is high clinical or radiological suspicion.…”

Section: Discussionmentioning

confidence: 99%

“…28 Studies have shown the predominance of these receptors in the lower respiratory tract and SARS CoV-2 having higher receptor tropism in the lower respiratory tract. 16,28 Although studies have a wide range of positivity, a pooled estimate of 11% suggests that BAL may be used to confirm SARS CoV-2 infection where nasopharyngeal specimens are negative, and there is high clinical or radiological suspicion.…”

Section: Discussionmentioning

confidence: 99%

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A systematic review and metanalysis of diagnostic yield of BAL for detection of SARS-CoV-2

Agrawal¹,

Goel

Gupta

et al. 2022

Heart & Lung

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Background The gold standard for diagnosing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is microbiological confirmation by reverse transcriptase-polymerase chain reaction (RT-PCR) 1 most commonly done using oropharyngeal (OP) and nasopharyngeal swabs (NP). But in suspected cases, where these samples are false-negative, bronchoalveolar lavage (BAL) may prove diagnostic. Objectives Hence, the the diagnostic yield of BAL for detection of SARS-CoV-2 in cases of non-diagnostic upper respiratory tract samples is reviewed Methods Databases such as MEDLINE, Scopus, and Google Scholar were searched using a systematic search strategy. The current study has been in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and has been registered with the International Prospective Registry of Systematic Reviews (CRD42020224088) Results 911 records were identified at initial database extraction, of which 317 duplicates were removed and, 596 records were screened for inclusion eligibility. We included total 19 studies in the systematic review, and 17 were included in metanalysis. The pooled estimate of SARS-CoV-2 positivity in BAL was 11% (95%CI: 0.01-0.24). A sensitivity analysis also showed that the results appear to be robust and minimal risk of bias amongst the studies Conclusion The current study demonstrates that BAL can be used to diagnose additional cases primary disease and superadded infections in patients with severe COVID-19 lower respiratory tract infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A systematic review and metanalysis of diagnostic yield of BAL for detection of SARS-CoV-2

Agrawal¹,

Goel

Gupta

et al. 2022

Heart & Lung

View full text Add to dashboard Cite

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“…Severe forms of COVID-19 are seemingly triggered by an immunological imbalance leading to severe acute respiratory syndrome (SARS) and cytokine storm [ 26 ]. ACE-2 receptor has a vital function in the pathogenesis of COVID-19, activating the coagulation system (causing thrombophilia), the renin-angiotensin system (leading to cardiovascular instability) and the kinine–kallikrein system (causing acute inflammatory lung oedema) [ 27 , 28 ]. Several manifestations of COVID-19, such as cardiovascular, kidney and brain symptoms, are associated with expression of ACE-2 and TMPRSS2 [ 29 – 31 ].…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal cancers, ACE-2/TMPRSS2 expression and susceptibility to COVID-19

et al. 2021

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Recent studies on the pathophysiology of COVID-19 are indicating that the Angiotensin convertase enzyme 2 (ACE-2) and transmembrane serine protease 2 (TMPRSS2) can act as a major component in the fusion of SARS-Cov-2 with target cells. It has also been observed that the expression of ACE-2 and TMPRSS2 can be altered in malignancies. Shedding light on this matter could be crucial since the COVID-19 pandemic interfered with many gastrointestinal cancer screening programs. Herein we discuss the possibility of severe forms of COVID-19 in patients with gastrointestinal cancers due to the gastrointestinal entry route of SARS-CoV-2 into the human body. The disruption of cancer screening programs caused by the current COVID-19 pandemic could therefore have massive negative health impact on patients affected by gastrointestinal malignancies.

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“…Furin is capable of cleaving and activating viral fusion proteins of HIV, Ebola [39], MERS-CoV [40], SARS-CoV [15], and SARS-CoV-2) [16] (Table 1). Furin accumulates mainly in the Golgi complex, but it can be transported to the cell surface via the endosomal pathway or can be released into the extracellular space [41]. For this reason, furin can cleave the S protein in the Golgi complex, and also in the extracellular space [38].…”

Section: Furin Primingmentioning

confidence: 99%

The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?

et al. 2021

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The interaction between the membrane spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the transmembrane angiotensin-converting enzyme 2 (ACE2) receptor of the human epithelial host cell is the first step of infection, which has a critical role for viral pathogenesis of the current coronavirus disease-2019 (COVID-19) pandemic. Following the binding between S1 subunit and ACE2 receptor, different serine proteases, including TMPRSS2 and furin, trigger and participate in the fusion of the viral envelope with the host cell membrane. On the basis of the high virulence and pathogenicity of SARS-CoV-2, other receptors have been found involved for viral binding and invasiveness of host cells. This review comprehensively discusses the mechanisms underlying the binding of SARS-CoV2 to ACE2 and putative alternative receptors, and the role of potential co-receptors and proteases in the early stages of SARS-CoV-2 infection. Given the short therapeutic time window within which to act to avoid the devastating evolution of the disease, we focused on potential therapeutic treatments—selected mainly among repurposing drugs—able to counteract the invasive front of proteases and mild inflammatory conditions, in order to prevent severe infection. Using existing approved drugs has the advantage of rapidly proceeding to clinical trials, low cost and, consequently, immediate and worldwide availability.

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Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury

Cited by 46 publications

References 359 publications

A systematic review and metanalysis of diagnostic yield of BAL for detection of SARS-CoV-2

A systematic review and metanalysis of diagnostic yield of BAL for detection of SARS-CoV-2

Gastrointestinal cancers, ACE-2/TMPRSS2 expression and susceptibility to COVID-19

The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?

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