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  1. AU="Zamai, Loris"
  2. AU=Kato Takashi
  3. AU=Haase Michael
  4. AU="Ingrams, Duncan"
  5. AU=Liu Rong
  6. AU="Musselman, Kristin E"
  7. AU=Abrams M J
  8. AU="Paul, Archi Sundar"
  9. AU=Yoon Hyuk
  10. AU="Gonzalez, Emily"
  11. AU="Dunnill, M S"
  12. AU=Kuo Chih-Hung
  13. AU=Geronimo Carly L.
  14. AU=Stafforini D M
  15. AU="Sytse J. Piersma"
  16. AU="Peng, Hongke"
  17. AU="Kelly, Geoffrey"
  18. AU=Schwartzenburg Joshua AU=Schwartzenburg Joshua
  19. AU="Deshpande, Sneha Satish"
  20. AU="Ganhewa, Aparna D" AU="Ganhewa, Aparna D"
  21. AU="Flanagan, T L"
  22. AU=Davila Eduardo
  23. AU="Miroli, Augusto"
  24. AU="Stahl, B"
  25. AU="Dehari, Hironari"
  26. AU="Pinheiro, Silviane Bezerra"
  27. AU="Jamal Al Deen Alkoteesh"
  28. AU="Chen, Dingqiang"
  29. AU="Jeremy C. Ganz"
  30. AU="Lee, Ta-Sheng"
  31. AU="Shi, Jin-Ming"
  32. AU=Kristoffersen K B
  33. AU=Du Chao
  34. AU="Anton I. Skaro"

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Treffer 1 - 10 von insgesamt 32

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  1. Artikel ; Online: Hypothesis: Efficacy of early treatments with some NSAIDs in COVID-19: Might it also depend on their direct and/or indirect zinc chelating ability?

    Zamai, Loris

    British journal of pharmacology

    2022  Band 180, Heft 3, Seite(n) 279–286

    Abstract: The present work argues for the involvement of the zinc chelating ability of some non-steroidal anti-inflammatory drugs as an additive mechanism able to increase their efficacy against COVID-19. ...

    Abstract The present work argues for the involvement of the zinc chelating ability of some non-steroidal anti-inflammatory drugs as an additive mechanism able to increase their efficacy against COVID-19.
    Mesh-Begriff(e) Humans ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; COVID-19 ; Zinc
    Chemische Substanzen Anti-Inflammatory Agents, Non-Steroidal ; Zinc (J41CSQ7QDS)
    Sprache Englisch
    Erscheinungsdatum 2022-12-08
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.15989
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  2. Artikel ; Online: Upregulation of the Renin-Angiotensin System Pathways and SARS-CoV-2 Infection: The Rationale for the Administration of Zinc-Chelating Agents in COVID-19 Patients.

    Zamai, Loris

    Cells

    2021  Band 10, Heft 3

    Abstract: The article describes the rationale for the administration of zinc-chelating agents in COVID-19 patients. In a previous work I have highlighted that the binding of the SARS-CoV spike proteins to the zinc-metalloprotease ACE2 has been shown to induce ACE2 ...

    Abstract The article describes the rationale for the administration of zinc-chelating agents in COVID-19 patients. In a previous work I have highlighted that the binding of the SARS-CoV spike proteins to the zinc-metalloprotease ACE2 has been shown to induce ACE2 shedding by activating the zinc-metalloprotease ADAM17, which ultimately leads to systemic upregulation of ACE2 activity. Moreover, based on experimental models, it was also shown the detrimental effect of the excessive systemic activity of ACE2 through its downstream pathways, which leads to "clinical" manifestations resembling COVID-19. In this regard, strong upregulation of circulating ACE2 activity was recently reported in COVID-19 patients, thus supporting the previous hypothesis that COVID-19 may derive from upregulation of ACE2 activity. Based on this, a reasonable hypothesis of using inhibitors that curb the upregulation of both ACE2 and ADAM17 zinc-metalloprotease activities and consequent positive feedback-loops (initially triggered by SARS-CoV-2 and subsequently sustained independently on viral trigger) is proposed as therapy for COVID-19. In particular, zinc-chelating agents such as citrate and ethylenediaminetetraacetic acid (EDTA) alone or in combination are expected to act in protecting from COVID-19 at different levels thanks to their both anticoagulant properties and inhibitory activity on zinc-metalloproteases. Several arguments are presented in support of this hypothesis and based on the current knowledge of both beneficial/harmful effects and cost/effectiveness, the use of chelating agents in the prevention and therapy of COVID-19 is proposed. In this regard, clinical trials (currently absent) employing citrate/EDTA in COVID-19 are urgently needed in order to shed more light on the efficacy of zinc chelators against SARS-CoV-2 infection in vivo.
    Mesh-Begriff(e) ADAM17 Protein/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Anticoagulants/pharmacology ; COVID-19/metabolism ; COVID-19/therapy ; Chelating Agents/pharmacology ; Citric Acid/pharmacology ; Drug Discovery ; Edetic Acid/pharmacology ; Humans ; Immunization, Passive/adverse effects ; Renin-Angiotensin System/drug effects ; SARS-CoV-2/drug effects ; Up-Regulation/drug effects ; Zinc/metabolism ; COVID-19 Serotherapy ; COVID-19 Drug Treatment
    Chemische Substanzen Anticoagulants ; Chelating Agents ; Citric Acid (2968PHW8QP) ; Edetic Acid (9G34HU7RV0) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; ADAM17 Protein (EC 3.4.24.86) ; ADAM17 protein, human (EC 3.4.24.86) ; Zinc (J41CSQ7QDS)
    Sprache Englisch
    Erscheinungsdatum 2021-02-27
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10030506
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Unveiling Human Non-Random Genome Editing Mechanisms Activated in Response to Chronic Environmental Changes: I. Where Might These Mechanisms Come from and What Might They Have Led To?

    Zamai, Loris

    Cells

    2020  Band 9, Heft 11

    Abstract: This article challenges the notion of the randomness of mutations in eukaryotic cells by unveiling stress-induced human non-random genome editing mechanisms. To account for the existence of such mechanisms, I have developed molecular concepts of the cell ...

    Abstract This article challenges the notion of the randomness of mutations in eukaryotic cells by unveiling stress-induced human non-random genome editing mechanisms. To account for the existence of such mechanisms, I have developed molecular concepts of the cell environment and cell environmental stressors and, making use of a large quantity of published data, hypothesised the origin of some crucial biological leaps along the evolutionary path of life on Earth under the pressure of natural selection, in particular, (1) virus-cell mating as a primordial form of sexual recombination and symbiosis; (2) Lamarckian CRISPR-Cas systems; (3) eukaryotic gene development; (4) antiviral activity of retrotransposon-guided mutagenic enzymes; and finally, (5) the exaptation of antiviral mutagenic mechanisms to stress-induced genome editing mechanisms directed at "hyper-transcribed" endogenous genes. Genes transcribed at their maximum rate (hyper-transcribed), yet still unable to meet new chronic environmental demands generated by "pollution", are inadequate and generate more and more intronic retrotransposon transcripts. In this scenario, RNA-guided mutagenic enzymes (e.g., Apolipoprotein B mRNA editing catalytic polypeptide-like enzymes, APOBECs), which have been shown to bind to retrotransposon RNA-repetitive sequences, would be surgically targeted by intronic retrotransposons on opened chromatin regions of the same "hyper-transcribed" genes. RNA-guided mutagenic enzymes may therefore "Lamarkianly" generate single nucleotide polymorphisms (SNP) and gene copy number variations (CNV), as well as transposon transposition and chromosomal translocations in the restricted areas of hyper-functional and inadequate genes, leaving intact the rest of the genome. CNV and SNP of hyper-transcribed genes may allow cells to surgically explore a new fitness scenario, which increases their adaptability to stressful environmental conditions. Like the mechanisms of immunoglobulin somatic hypermutation, non-random genome editing mechanisms may generate several cell mutants, and those codifying for the most environmentally adequate proteins would have a survival advantage and would therefore be Darwinianly selected. Non-random genome editing mechanisms represent tools of evolvability leading to organismal adaptation including transgenerational non-Mendelian gene transmission or to death of environmentally inadequate genomes. They are a link between environmental changes and biological novelty and plasticity, finally providing a molecular basis to reconcile gene-centred and "ecological" views of evolution.
    Mesh-Begriff(e) APOBEC Deaminases/metabolism ; CRISPR-Cas Systems/genetics ; Environment ; Gene Editing ; Genome, Human ; Humans ; Mutation/genetics
    Chemische Substanzen APOBEC Deaminases (EC 3.5.4.5)
    Sprache Englisch
    Erscheinungsdatum 2020-10-27
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9112362
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: The Yin and Yang of ACE/ACE2 Pathways: The Rationale for the Use of Renin-Angiotensin System Inhibitors in COVID-19 Patients.

    Zamai, Loris

    Cells

    2020  Band 9, Heft 7

    Abstract: The article describes the rationale for inhibition of the renin-angiotensin system (RAS) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent positive feedback-loop mechanisms. Based purely on experimental studies in which ... ...

    Abstract The article describes the rationale for inhibition of the renin-angiotensin system (RAS) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent positive feedback-loop mechanisms. Based purely on experimental studies in which RAS pathway inhibitors were administered in vivo to humans/rodents, a reasonable hypothesis of using inhibitors that block both ACE and ACE2 zinc metalloproteases and their downstream pathways in COVID-19 patients will be proposed. In particular, metal (zinc) chelators and renin inhibitors may work alone or in combination to inhibit the positive feedback loops (initially triggered by SARS-CoV-2 and subsequently sustained by hypoxia independently on viral trigger) as both arms of renin-angiotensin system are upregulated, leading to critical, advanced and untreatable stages of the disease.
    Mesh-Begriff(e) Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Angiotensins/metabolism ; Betacoronavirus/drug effects ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/metabolism ; Coronavirus Infections/physiopathology ; Feedback, Physiological/drug effects ; Humans ; Pandemics ; Peptidyl-Dipeptidase A/adverse effects ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/metabolism ; Pneumonia, Viral/physiopathology ; Renin-Angiotensin System/drug effects ; Renin-Angiotensin System/genetics ; Renin-Angiotensin System/physiology ; Risk Factors ; SARS-CoV-2
    Chemische Substanzen Angiotensin-Converting Enzyme Inhibitors ; Angiotensins ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2020-07-16
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9071704
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel: The Yin and Yang of ACE/ACE2 Pathways: The Rationale for the Use of Renin-Angiotensin System Inhibitors in COVID-19 Patients

    Zamai, Loris

    Cells

    Abstract: The article describes the rationale for inhibition of the renin-angiotensin system (RAS) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent positive feedback-loop mechanisms Based purely on experimental studies in which ... ...

    Abstract The article describes the rationale for inhibition of the renin-angiotensin system (RAS) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent positive feedback-loop mechanisms Based purely on experimental studies in which RAS pathway inhibitors were administered in vivo to humans/rodents, a reasonable hypothesis of using inhibitors that block both ACE and ACE2 zinc metalloproteases and their downstream pathways in COVID-19 patients will be proposed In particular, metal (zinc) chelators and renin inhibitors may work alone or in combination to inhibit the positive feedback loops (initially triggered by SARS-CoV-2 and subsequently sustained by hypoxia independently on viral trigger) as both arms of renin-angiotensin system are upregulated, leading to critical, advanced and untreatable stages of the disease
    Schlagwörter covid19
    Verlag WHO
    Dokumenttyp Artikel
    Anmerkung WHO #Covidence: #654981
    Datenquelle COVID19

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  6. Artikel ; Online: The Yin and Yang of ACE/ACE2 Pathways

    Zamai, Loris

    The Rationale for the Use of Renin-Angiotensin System Inhibitors in COVID-19 Patients

    2020  

    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsland it
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Volltext online

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  7. Artikel ; Online: Hypothesis: Possible influence of antivector immunity and SARS-CoV-2 variants on efficacy of ChAdOx1 nCoV-19 vaccine.

    Zamai, Loris / Rocchi, Marco B L

    British journal of pharmacology

    2021  Band 179, Heft 2, Seite(n) 218–226

    Abstract: The present work provides arguments for the involvement of anti-vector immunity and of SARS-CoV-2 variants on the efficacy of ChAdOx1 nCoV-19 vaccine. First, it is suggested that anti-vector immunity takes place as homologous vaccination with ChAdOx1 ... ...

    Abstract The present work provides arguments for the involvement of anti-vector immunity and of SARS-CoV-2 variants on the efficacy of ChAdOx1 nCoV-19 vaccine. First, it is suggested that anti-vector immunity takes place as homologous vaccination with ChAdOx1 nCoV-19 vaccine is applied and interferes with vaccine efficacy when the interval between prime and booster doses is less than 3 months. Second, longitudinal studies suggest that ChAdOx1 nCoV-19 vaccine provides suboptimal efficacy against SARS-CoV-2 Alpha variant, which appears to have an increased transmissibility among vaccinated people. At the moment, ChAdOx1 nCoV-19 vaccine is able to reduce the severity of symptoms and transmissibility. However, if the vaccinated individuals do not maintain physical preventive measures, they could turn into potential spreaders, thus suggesting that mass vaccination will not quickly solve the pandemic. Possible consequences of SARS-CoV-2 evolution and of repeated anti-SARS-CoV-2 vaccinations are discussed and adoption of an influenza-like vaccination strategy is suggested.
    Mesh-Begriff(e) COVID-19 ; COVID-19 Vaccines ; ChAdOx1 nCoV-19 ; Humans ; SARS-CoV-2 ; Vaccine Efficacy
    Chemische Substanzen COVID-19 Vaccines ; ChAdOx1 nCoV-19 (B5S3K2V0G8)
    Sprache Englisch
    Erscheinungsdatum 2021-07-31
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.15620
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  8. Artikel ; Online: Circulating ACE2 level and zinc/albumin ratio as potential biomarkers for a precision medicine approach to COVID-19.

    Benedetti, Serena / Sisti, Davide / Vandini, Daniela / Barocci, Simone / Sudano, Maurizio / Carlotti, Eugenio / Teng, Jade Lee Lee / Zamai, Loris

    Advances in biological regulation

    2023  Band 89, Seite(n) 100973

    Abstract: Highly mutable influenza is successfully countered based on individual susceptibility and similar precision-like medicine approach should be effective against SARS-COV-2. Among predictive markers to bring precision medicine to COVID-19, circulating ACE2 ... ...

    Abstract Highly mutable influenza is successfully countered based on individual susceptibility and similar precision-like medicine approach should be effective against SARS-COV-2. Among predictive markers to bring precision medicine to COVID-19, circulating ACE2 has potential features being upregulated in both severe COVID-19 and predisposing comorbidities. Spike SARS-CoVs were shown to induce ADAM17-mediated shedding of enzymatic active ACE2, thus accounting for its increased activity that has also been suggested to induce positive feedback loops leading to COVID-19-like manifestations. For this reason, pre-existing ACE2 activity and inhibition of ACE2/ADAM17 zinc-metalloproteases through zinc chelating agents have been proposed to predict COVID-19 outcome before infection and to protect from COVID-19, respectively. Since most diagnostic laboratories are not equipped for enzymatic activity determination, other potential predictive markers of disease progression exploitable by diagnostic laboratories were explored. Concentrations of circulating albumin, zinc, ACE2 protein and its activity were investigated in healthy, diabetic (COVID-19-susceptible) and SARS-CoV-2-negative COVID-19 individuals. ACE2 both protein levels and activity significantly increased in COVID-19 and diabetic patients. Abnormal high levels of ACE2 characterised a subgroup (16-19%) of diabetics, while COVID-19 patients were characterised by significantly higher zinc/albumin ratios, pointing to a relative increase of albumin-unbound zinc species, such as free zinc ones. Data on circulating ACE2 levels are in line with the hypothesis that they can drive susceptibility to COVID-19 and elevated zinc/albumin ratios support the therapeutic use of zinc chelating inhibitors of ACE2/ADAM17 zinc-metalloproteases in a targeted therapy for COVID-19.
    Mesh-Begriff(e) Humans ; COVID-19/genetics ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; Renin-Angiotensin System/physiology ; Angiotensin-Converting Enzyme 2/genetics ; Peptidyl-Dipeptidase A ; Precision Medicine ; Zinc/therapeutic use ; Albumins/metabolism ; Biomarkers
    Chemische Substanzen Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Zinc (J41CSQ7QDS) ; Albumins ; Biomarkers
    Sprache Englisch
    Erscheinungsdatum 2023-05-23
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2667413-0
    ISSN 2212-4934 ; 2212-4926
    ISSN (online) 2212-4934
    ISSN 2212-4926
    DOI 10.1016/j.jbior.2023.100973
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: ESCCABase project: A repository in progress.

    Ortolani, Claudio / D'Atri, Mario / Zamai, Loris / Canonico, Barbara / Del Zotto, Genny / Papa, Stefano

    Cytometry. Part A : the journal of the International Society for Analytical Cytology

    2021  Band 99, Heft 7, Seite(n) 659–663

    Mesh-Begriff(e) Databases, Factual
    Sprache Englisch
    Erscheinungsdatum 2021-05-07
    Erscheinungsland United States
    Dokumenttyp Editorial
    ZDB-ID 2099868-5
    ISSN 1552-4930 ; 0196-4763 ; 1552-4922
    ISSN (online) 1552-4930
    ISSN 0196-4763 ; 1552-4922
    DOI 10.1002/cyto.a.24355
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Which ones, when and why should renin-angiotensin system inhibitors work against COVID-19?

    Montanari, Mariele / Canonico, Barbara / Nordi, Evelyn / Vandini, Daniela / Barocci, Simone / Benedetti, Serena / Carlotti, Eugenio / Zamai, Loris

    Advances in biological regulation

    2021  Band 81, Seite(n) 100820

    Abstract: The article describes the possible pathophysiological origin of COVID-19 and the crucial role of renin-angiotensin system (RAS), providing several "converging" evidence in support of this hypothesis. SARS-CoV-2 has been shown to initially upregulate ACE2 ...

    Abstract The article describes the possible pathophysiological origin of COVID-19 and the crucial role of renin-angiotensin system (RAS), providing several "converging" evidence in support of this hypothesis. SARS-CoV-2 has been shown to initially upregulate ACE2 systemic activity (early phase), which can subsequently induce compensatory responses leading to upregulation of both arms of the RAS (late phase) and consequently to critical, advanced and untreatable stages of COVID-19 disease. The main and initial actors of the process are ACE2 and ADAM17 zinc-metalloproteases, which, initially triggered by SARS-CoV-2 spike proteins, work together in increasing circulating Ang 1-7 and Ang 1-9 peptides and downstream (Mas and Angiotensin type 2 receptors) pathways with anti-inflammatory, hypotensive and antithrombotic activities. During the late phase of severe COVID-19, compensatory secretion of renin and ACE enzymes are subsequently upregulated, leading to inflammation, hypertension and thrombosis, which further sustain ACE2 and ADAM17 upregulation. Based on this hypothesis, COVID-19-phase-specific inhibition of different RAS enzymes is proposed as a pharmacological strategy against COVID-19 and vaccine-induced adverse effects. The aim is to prevent the establishment of positive feedback-loops, which can sustain hyperactivity of both arms of the RAS independently of viral trigger and, in some cases, may lead to Long-COVID syndrome.
    Mesh-Begriff(e) ADAM17 Protein/antagonists & inhibitors ; ADAM17 Protein/biosynthesis ; Angiotensin I/metabolism ; Angiotensin-Converting Enzyme 2/antagonists & inhibitors ; Angiotensin-Converting Enzyme 2/biosynthesis ; COVID-19/metabolism ; Gene Expression Regulation, Enzymologic ; Humans ; Peptide Fragments/metabolism ; Renin-Angiotensin System ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/antagonists & inhibitors ; Spike Glycoprotein, Coronavirus/metabolism ; Up-Regulation ; COVID-19 Drug Treatment
    Chemische Substanzen Peptide Fragments ; Spike Glycoprotein, Coronavirus ; angiotensin I (1-9) ; spike protein, SARS-CoV-2 ; Angiotensin I (9041-90-1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; ADAM17 Protein (EC 3.4.24.86) ; ADAM17 protein, human (EC 3.4.24.86) ; angiotensin I (1-7) (IJ3FUK8MOF)
    Sprache Englisch
    Erscheinungsdatum 2021-08-12
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2667413-0
    ISSN 2212-4934 ; 2212-4926
    ISSN (online) 2212-4934
    ISSN 2212-4926
    DOI 10.1016/j.jbior.2021.100820
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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