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 journalArticlepeer-review

13 Scopus citations


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 languageAmerican English
Article number101384
Issue number8
StatePublished - 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 .

Publisher Copyright:
© 2020 The Authors


  • Classification of Proteins
  • Evolutionary Mechanisms
  • Virology


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