Thymosin-α1 binds with ACE and downregulates the expression of ACE2 in human respiratory epithelia.

Background: Thymosin-α1 has been implicated into the treatment of novel respiratory virus Coronavirus Disease 2019 (COVID-19), but the underlying mechanisms are still disputable.

Aim: Herein we aimed to reveal a previously unrecognized mechanism that thymosin-α1 prevents COVID-19 by binding with angiotensin-converting enzyme (ACE), which was inspired from the tool of network pharmacology.

Methods: KEGG pathway enrichment of thymosin-α1 treating COVID-19 was analyzed by Database of Functional Annotation Bioinformatics Microarray Analysis, then core targets were validated by ligand binding kinetics assay and fluorometric detection of ACE and ACE2 enzymatic activity.