The Rationale for Angiotensin Receptor Neprilysin Inhibitors in a Multi-Targeted Therapeutic Approach to COVID-19
| العنوان: | The Rationale for Angiotensin Receptor Neprilysin Inhibitors in a Multi-Targeted Therapeutic Approach to COVID-19 |
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| المؤلفون: | Alessandro Bellis, Ciro Mauro, Carmine Morisco, Emanuele Barbato, Bruno Trimarco |
| المساهمون: | Bellis, A., Mauro, C., Barbato, E., Trimarco, B., Morisco, C. |
| المصدر: | International Journal of Molecular Sciences, Vol 21, Iss 8612, p 8612 (2020) International Journal of Molecular Sciences |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Angiotensin receptor, Tetrazoles, Review, Substance P, 030204 cardiovascular system & hematology, Pharmacology, angiotensin II, Sacubitril, lcsh:Chemistry, Adrenomedullin, 0302 clinical medicine, Drug Combination, 030212 general & internal medicine, Neprilysin, lcsh:QH301-705.5, Tetrazole, Spectroscopy, Angiotensin Receptor Antagonists, Aminobutyrates, Angiotensin Receptor Antagonist, General Medicine, Computer Science Applications, Drug Combinations, Valsartan, apelin, Angiotensin-converting enzyme 2, Coronavirus Infections, Human, medicine.drug, Aminobutyrate, Pneumonia, Viral, Catalysis, neprilysin, Inorganic Chemistry, 03 medical and health sciences, medicine, Animals, Humans, Sacubitril/valsartan, Physical and Theoretical Chemistry, Pandemics, Molecular Biology, Pandemic, natriuretic peptide, Animal, Coronavirus Infection, business.industry, Biphenyl Compounds, Organic Chemistry, fungi, COVID-19, Angiotensin II, lcsh:Biology (General), lcsh:QD1-999, bradykinin, business, Sacubitril, Valsartan |
| الوصف: | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) determines the angiotensin converting enzyme 2 (ACE2) down-regulation and related decrease in angiotensin II degradation. Both these events trigger “cytokine storm” leading to acute lung and cardiovascular injury. A selective therapy for COVID-19 has not yet been identified. Clinical trials with remdesivir gave discordant results. Thus, healthcare systems have focused on “multi-targeted” therapeutic strategies aiming at relieving systemic inflammation and thrombotic complications. No randomized clinical trial has demonstrated the efficacy of renin angiotensin system antagonists in reducing inflammation related to COVID-19. Dexamethasone and tocilizumab showed encouraging data, but their use needs to be further validated. The still-controversial efficacy of these treatments highlighted the importance of organ injury prevention in COVID-19. Neprilysin (NEP) might be an interesting target for this purpose. NEP expression is increased by cytokines on lung fibroblasts surface. NEP activity is elevated in acute respiratory distress syndrome and it is conceivable that it is also high in COVID-19. NEP is implicated in the degradation of natriuretic peptides, bradykinin, substance P, adrenomedullin, and apelin that account for prevention of organ injury. Thus, NEP/angiotensin receptor type 1 (AT1R) inhibitor sacubitril/valsartan (SAC/VAL) may increase levels of these molecules and block AT1Rs required for ACE2 endocytosis in SARS-CoV-2 infection. Moreover, SAC/VAL has a positive impact on acute heart failure that is very frequently observed in deceased COVID-19 patients. The current review aims to summarize actual therapeutic strategies for COVID-19 and to examine the data supporting the potential benefits of SAC/VAL in COVID-19 treatment. |
| اللغة: | English |
| تدمد: | 1661-6596 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b025a2e87298d22525ce7270a1a62abTest https://www.mdpi.com/1422-0067/21/22/8612Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2b025a2e87298d22525ce7270a1a62ab |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16616596 14220067 |
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