ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic
| Autor: | Alexander Vainstein, Maya Braun, Shmuel Benenson, Elad Sharon, Maya Miller, Yuval Tabach, Irene Unterman, Anna Mellul Shtern |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Coronavirus disease 2019 (COVID-19) NSAIDs vasodilators Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spillover infection COX-inhibitors 02 engineering and technology Computational biology Disease Biology Article Evolutionary Mechanisms 03 medical and health sciences phylogenetic profiling Virology Intervention (counseling) evolution Pandemic Computational analysis lcsh:Science Multidisciplinary SARS-CoV-2 COVID-19 021001 nanoscience & nanotechnology 030104 developmental biology lcsh:Q 0210 nano-technology Classification of Proteins Protein network hormones hormone substitutes and hormone antagonists |
| Zdroj: | iScience, Vol 23, Iss 8, Pp 101384-(2020) iScience |
| ISSN: | 2589-0042 |
| DOI: | 10.1016/j.isci.2020.101384 |
| Popis: | 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 1671 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 perturbate the ACE2 network affecting infectivity as well as the pathophysiology of the disease. Graphical Abstract Highlights - Mapping the ACE2 conservation pattern in 146 mammal reservoirs and 1671 eukaryotes - Identification of genes that show a similar evolutionary pattern as ACE2 - Generation of an ACE2 protein network using co-evolution and data integration - Drugs-to-network analyses mapped 145 drugs that perturbated the ACE2 network |
| Databáze: | OpenAIRE |
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