ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic

Maya Braun; Elad Sharon; Irene Unterman; Maya Miller; Anna Mellul Shtern; Shmuel Benenson; Alexander Vainstein; Yuval Tabach

doi:10.1016/j.isci.2020.101384

ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic

Maya Braun, Elad Sharon, Irene Unterman, Maya Miller, Anna Mellul Shtern, Shmuel Benenson, Alexander Vainstein, Yuval Tabach^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

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.

Original language	English
Article number	101384
Journal	iScience
Volume	23
Issue number	8
DOIs	https://doi.org/10.1016/j.isci.2020.101384
State	Published - 21 Aug 2020

Bibliographical note

Funding Information:
Funding was received from the Israel Science Foundation (grant agreement 1591/19 ), and the Israel Innovation Authority under the R&D Plans of Industrial Products for the Prevention and Treatment of the COVID-19 (grant agreement 70273 ). The graphical abstract was created by BioRender.com .

Publisher Copyright:
© 2020 The Authors

Keywords

Classification of Proteins
Evolutionary Mechanisms
Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.isci.2020.101384

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abstract = "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.",

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AU - Shtern, Anna Mellul

AU - Benenson, Shmuel

AU - Vainstein, Alexander

AU - Tabach, Yuval

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ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

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