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

Area of Science:

• Genomics
• Virology
• Drug Discovery

Background:

• The SARS-CoV-2 pandemic highlights the need to understand virus-host interactions.
• Angiotensin-Converting Enzyme 2 (ACE2) is crucial for SARS-CoV-2 cell entry and understanding coronavirus zoonosis.
• Research into ACE2 is vital for developing novel antiviral drugs.

Purpose of the Study:

• To systematically analyze the conservation and co-evolution of the ACE2 protein network in eukaryotes.
• To identify potential drug targets within the ACE2 co-evolved protein network.
• To investigate existing drugs that may affect SARS-CoV-2 infectivity and disease pathophysiology.

Main Methods:

• Performed a systematic analysis of ACE2 conservation across 1,671 eukaryotic species.
• Utilized data integration from multiple sources to identify the co-evolved protein network.
• Employed computational analysis to pinpoint drugs targeting the identified network.

Main Results:

• Discovered unexpected ACE2 conservation patterns in metazoans, plants, fungi, and protists.
• Identified a co-evolved protein network associated with ACE2.
• Found that widely used drugs, including nonsteroidal anti-inflammatory drugs and vasodilators, target this network.

Conclusions:

• The ACE2 network exhibits conserved patterns across diverse eukaryotic organisms.
• Existing drugs targeting the ACE2 network may influence SARS-CoV-2 infectivity.
• These findings offer potential therapeutic strategies for COVID-19 by repurposing known drugs.