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

7 Pages Posted: 21 Apr 2020 Publication Status: Published

See all articles by Maya Braun

Maya Braun

Hebrew University of Jerusalem - Department of Developmental Biology and Cancer Research

Elad Sharon

Hebrew University of Jerusalem - Department of Developmental Biology and Cancer Research

Irene Unterman

Hebrew University of Jerusalem - Department of Developmental Biology and Cancer Research

Maya Miller

Hebrew University of Jerusalem - Department of Developmental Biology and Cancer Research

Anna Shtern Mellul

Hebrew University of Jerusalem - Department of Developmental Biology and Cancer Research

Shmuel Benenson

Hebrew University of Jerusalem - Department of Clinical Microbiology and Infectious Diseases

Yuval Tabach

Hebrew University of Jerusalem - Department of Developmental Biology and Cancer Research

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Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spillover infection on 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 generated a list of drugs that target this network by using the entire human proteomes. 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. Millions of patients might benefit.

Note: Funding: Funding was received from the Israel Science Foundation (ISF) (grant agreement 1591/19).

Conflict of Interest: The authors declare no competing interests.

Keywords: COVID-19, SARS-CoV-2, Phylogenetic profiling, evolution, ACE2, NSAIDs

Suggested Citation

Braun, Maya and Sharon, Elad and Unterman, Irene and Miller, Maya and Shtern Mellul, Anna and Benenson, Shmuel and Tabach, Yuval, ACE2 Co-Evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic. Available at SSRN: https://ssrn.com/abstract=3578139 or http://dx.doi.org/10.2139/ssrn.3578139
This version of the paper has not been formally peer reviewed.

Maya Braun

Hebrew University of Jerusalem - Department of Developmental Biology and Cancer Research ( email )

Jerusalem
Israel

Elad Sharon

Hebrew University of Jerusalem - Department of Developmental Biology and Cancer Research ( email )

Jerusalem
Israel

Irene Unterman

Hebrew University of Jerusalem - Department of Developmental Biology and Cancer Research ( email )

Jerusalem
Israel

Maya Miller

Hebrew University of Jerusalem - Department of Developmental Biology and Cancer Research ( email )

Jerusalem
Israel

Anna Shtern Mellul

Hebrew University of Jerusalem - Department of Developmental Biology and Cancer Research ( email )

Jerusalem
Israel

Shmuel Benenson

Hebrew University of Jerusalem - Department of Clinical Microbiology and Infectious Diseases ( email )

Israel

Yuval Tabach (Contact Author)

Hebrew University of Jerusalem - Department of Developmental Biology and Cancer Research ( email )

Jerusalem
Israel

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