ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic
Summary: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spillover infection in December 2019 has caused an unprecedented pandemic. SARS-CoV-2, as other coronaviruses, binds its target cells through the angiotensin-converting enzyme 2 (ACE2) receptor. Accordingly, this makes ACE2 re...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-08-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220305721 |
| _version_ | 1818209935213723648 |
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| author | Maya Braun Elad Sharon Irene Unterman Maya Miller Anna Mellul Shtern Shmuel Benenson Alexander Vainstein Yuval Tabach |
| author_facet | Maya Braun Elad Sharon Irene Unterman Maya Miller Anna Mellul Shtern Shmuel Benenson Alexander Vainstein Yuval Tabach |
| author_sort | Maya Braun |
| collection | DOAJ |
| description | Summary: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spillover infection in December 2019 has caused an unprecedented pandemic. SARS-CoV-2, as other coronaviruses, binds its target cells through the angiotensin-converting enzyme 2 (ACE2) receptor. Accordingly, this makes ACE2 research essential for understanding the zoonotic nature of coronaviruses and identifying novel drugs. Here we present a systematic analysis of the ACE2 conservation and co-evolution protein network across 1,671 eukaryotes, revealing an unexpected conservation pattern in specific metazoans, plants, fungi, and protists. We identified the co-evolved protein network and pinpointed a list of drugs that target this network by using data integration from different sources. Our computational analysis found widely used drugs such as nonsteroidal anti-inflammatory drugs and vasodilators. These drugs are expected to perturb the ACE2 network affecting infectivity as well as the pathophysiology of the disease. |
| first_indexed | 2024-12-12T05:08:37Z |
| format | Article |
| id | doaj.art-74a00845948d4d16ba722580c4ac73a6 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-12T05:08:37Z |
| publishDate | 2020-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-74a00845948d4d16ba722580c4ac73a62022-12-22T00:37:00ZengElsevieriScience2589-00422020-08-01238101384ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 PandemicMaya Braun0Elad Sharon1Irene Unterman2Maya Miller3Anna Mellul Shtern4Shmuel Benenson5Alexander Vainstein6Yuval Tabach7Department of Developmental Biology and Cancer Research, Institute of Medical Research - Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, IsraelDepartment of Developmental Biology and Cancer Research, Institute of Medical Research - Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel; Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, IsraelDepartment of Developmental Biology and Cancer Research, Institute of Medical Research - Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, IsraelDepartment of Developmental Biology and Cancer Research, Institute of Medical Research - Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, IsraelDepartment of Developmental Biology and Cancer Research, Institute of Medical Research - Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, IsraelDepartment of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, IsraelRobert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, IsraelDepartment of Developmental Biology and Cancer Research, Institute of Medical Research - Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel; Corresponding authorSummary: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spillover infection in December 2019 has caused an unprecedented pandemic. SARS-CoV-2, as other coronaviruses, binds its target cells through the angiotensin-converting enzyme 2 (ACE2) receptor. Accordingly, this makes ACE2 research essential for understanding the zoonotic nature of coronaviruses and identifying novel drugs. Here we present a systematic analysis of the ACE2 conservation and co-evolution protein network across 1,671 eukaryotes, revealing an unexpected conservation pattern in specific metazoans, plants, fungi, and protists. We identified the co-evolved protein network and pinpointed a list of drugs that target this network by using data integration from different sources. Our computational analysis found widely used drugs such as nonsteroidal anti-inflammatory drugs and vasodilators. These drugs are expected to perturb the ACE2 network affecting infectivity as well as the pathophysiology of the disease.http://www.sciencedirect.com/science/article/pii/S2589004220305721Classification of ProteinsEvolutionary MechanismsVirology |
| spellingShingle | Maya Braun Elad Sharon Irene Unterman Maya Miller Anna Mellul Shtern Shmuel Benenson Alexander Vainstein Yuval Tabach ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic iScience Classification of Proteins Evolutionary Mechanisms Virology |
| title | ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic |
| title_full | ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic |
| title_fullStr | ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic |
| title_full_unstemmed | ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic |
| title_short | ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic |
| title_sort | ace2 co evolutionary pattern suggests targets for pharmaceutical intervention in the covid 19 pandemic |
| topic | Classification of Proteins Evolutionary Mechanisms Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220305721 |
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