Application of System Biology to Explore the Association of Neprilysin, Angiotensin-Converting Enzyme 2 (ACE2), and Carbonic Anhydrase (CA) in Pathogenesis of SARS-CoV-2
Abstract Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears with common symptoms including fever, dry cough, and fatigue, as well as some less common sysmptoms such as loss of taste and smell, diarrhea, skin rashes and dis...
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Biological Procedures Online |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12575-020-00124-6 |
| _version_ | 1811224459823022080 |
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| author | Reza Zolfaghari Emameh Reza Falak Elham Bahreini |
| author_facet | Reza Zolfaghari Emameh Reza Falak Elham Bahreini |
| author_sort | Reza Zolfaghari Emameh |
| collection | DOAJ |
| description | Abstract Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears with common symptoms including fever, dry cough, and fatigue, as well as some less common sysmptoms such as loss of taste and smell, diarrhea, skin rashes and discoloration of fingers. COVID-19 patients may also suffer from serious symptoms including shortness of breathing, chest pressure and pain, as well as loss of daily routine habits, pointing out to a sever reduction in the quality of life. COVID-19 has afftected almost all countries, however, the United States contains the highest number of infection (> 1,595,000 cases) and deaths cases (> 95,000 deaths) in the world until May 21, 2020. Finding an influential treatment strategy against COVID-19 can be facilitated through better understanding of the virus pathogenesis and consequently interrupting the biochemical pathways that the virus may play role in human body as the current reservoir of the virus. Results In this study, we combined system biology and bioinformatic approaches to define the role of coexpression of angiotensin-converting enzyme 2 (ACE2), neprilysin or membrane metallo-endopeptidase (MME), and carbonic anhydrases (CAs) and their association in the pathogenesis of SARS-CoV-2. The results revealed that ACE2 as the cellular attachment site of SARS-CoV-2, neprilysin, and CAs have a great contribution together in the renin angiotensin system (RAS) and consequently in pathogenesis of SARS-CoV-2 in the vital organs such as respiratory, renal, and blood circulation systems. Any disorder in neprilysin, ACE2, and CAs can lead to increase of CO2 concentration in blood and respiratory acidosis, induction of pulmonary edema and heart and renal failures. Conclusions Due to the presence of ACE2-Neprilysin-CA complex in most of vital organs and as a receptor of COVID-19, it is expected that most organs are affected by SARS-CoV-2 such as inflammation and fibrosis of lungs, which may conversely affect their vital functions, temporary or permanently, sometimes leading to death. Therefore, ACE2-Neprilysin-CA complex could be the key factor of pathogenesis of SARS-CoV-2 and may provide us useful information to find better provocative and therapeutic strategies against COVID-19. |
| first_indexed | 2024-04-12T08:49:46Z |
| format | Article |
| id | doaj.art-c5c5f837ca3a4195a850717228e20859 |
| institution | Directory Open Access Journal |
| issn | 1480-9222 |
| language | English |
| last_indexed | 2024-04-12T08:49:46Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Procedures Online |
| spelling | doaj.art-c5c5f837ca3a4195a850717228e208592022-12-22T03:39:37ZengBMCBiological Procedures Online1480-92222020-06-012211910.1186/s12575-020-00124-6Application of System Biology to Explore the Association of Neprilysin, Angiotensin-Converting Enzyme 2 (ACE2), and Carbonic Anhydrase (CA) in Pathogenesis of SARS-CoV-2Reza Zolfaghari Emameh0Reza Falak1Elham Bahreini2Department of Energy and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB)Immunology Research Center, Iran University of Medical SciencesDepartment of Biochemistry, Faculty of Medicine, Iran University of Medical SciencesAbstract Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears with common symptoms including fever, dry cough, and fatigue, as well as some less common sysmptoms such as loss of taste and smell, diarrhea, skin rashes and discoloration of fingers. COVID-19 patients may also suffer from serious symptoms including shortness of breathing, chest pressure and pain, as well as loss of daily routine habits, pointing out to a sever reduction in the quality of life. COVID-19 has afftected almost all countries, however, the United States contains the highest number of infection (> 1,595,000 cases) and deaths cases (> 95,000 deaths) in the world until May 21, 2020. Finding an influential treatment strategy against COVID-19 can be facilitated through better understanding of the virus pathogenesis and consequently interrupting the biochemical pathways that the virus may play role in human body as the current reservoir of the virus. Results In this study, we combined system biology and bioinformatic approaches to define the role of coexpression of angiotensin-converting enzyme 2 (ACE2), neprilysin or membrane metallo-endopeptidase (MME), and carbonic anhydrases (CAs) and their association in the pathogenesis of SARS-CoV-2. The results revealed that ACE2 as the cellular attachment site of SARS-CoV-2, neprilysin, and CAs have a great contribution together in the renin angiotensin system (RAS) and consequently in pathogenesis of SARS-CoV-2 in the vital organs such as respiratory, renal, and blood circulation systems. Any disorder in neprilysin, ACE2, and CAs can lead to increase of CO2 concentration in blood and respiratory acidosis, induction of pulmonary edema and heart and renal failures. Conclusions Due to the presence of ACE2-Neprilysin-CA complex in most of vital organs and as a receptor of COVID-19, it is expected that most organs are affected by SARS-CoV-2 such as inflammation and fibrosis of lungs, which may conversely affect their vital functions, temporary or permanently, sometimes leading to death. Therefore, ACE2-Neprilysin-CA complex could be the key factor of pathogenesis of SARS-CoV-2 and may provide us useful information to find better provocative and therapeutic strategies against COVID-19.http://link.springer.com/article/10.1186/s12575-020-00124-6SARS-CoV-2COVID-19Angiotensin-converting enzyme 2 (ACE2)NeprilysinCarbonic anhydrases (CAs)Renin angiotensin system (RAS) |
| spellingShingle | Reza Zolfaghari Emameh Reza Falak Elham Bahreini Application of System Biology to Explore the Association of Neprilysin, Angiotensin-Converting Enzyme 2 (ACE2), and Carbonic Anhydrase (CA) in Pathogenesis of SARS-CoV-2 Biological Procedures Online SARS-CoV-2 COVID-19 Angiotensin-converting enzyme 2 (ACE2) Neprilysin Carbonic anhydrases (CAs) Renin angiotensin system (RAS) |
| title | Application of System Biology to Explore the Association of Neprilysin, Angiotensin-Converting Enzyme 2 (ACE2), and Carbonic Anhydrase (CA) in Pathogenesis of SARS-CoV-2 |
| title_full | Application of System Biology to Explore the Association of Neprilysin, Angiotensin-Converting Enzyme 2 (ACE2), and Carbonic Anhydrase (CA) in Pathogenesis of SARS-CoV-2 |
| title_fullStr | Application of System Biology to Explore the Association of Neprilysin, Angiotensin-Converting Enzyme 2 (ACE2), and Carbonic Anhydrase (CA) in Pathogenesis of SARS-CoV-2 |
| title_full_unstemmed | Application of System Biology to Explore the Association of Neprilysin, Angiotensin-Converting Enzyme 2 (ACE2), and Carbonic Anhydrase (CA) in Pathogenesis of SARS-CoV-2 |
| title_short | Application of System Biology to Explore the Association of Neprilysin, Angiotensin-Converting Enzyme 2 (ACE2), and Carbonic Anhydrase (CA) in Pathogenesis of SARS-CoV-2 |
| title_sort | application of system biology to explore the association of neprilysin angiotensin converting enzyme 2 ace2 and carbonic anhydrase ca in pathogenesis of sars cov 2 |
| topic | SARS-CoV-2 COVID-19 Angiotensin-converting enzyme 2 (ACE2) Neprilysin Carbonic anhydrases (CAs) Renin angiotensin system (RAS) |
| url | http://link.springer.com/article/10.1186/s12575-020-00124-6 |
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