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

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.