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
Affiliations
Maya Braun
Department of Developmental Biology and Cancer Research, Institute of Medical Research - Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
Elad Sharon
Department 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, Israel
Irene Unterman
Department of Developmental Biology and Cancer Research, Institute of Medical Research - Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
Maya Miller
Department of Developmental Biology and Cancer Research, Institute of Medical Research - Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
Anna Mellul Shtern
Department of Developmental Biology and Cancer Research, Institute of Medical Research - Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
Shmuel Benenson
Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Alexander Vainstein
Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel
Yuval Tabach
Department of Developmental Biology and Cancer Research, Institute of Medical Research - Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel; Corresponding author
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.
