Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.13.248351v1?rss=1 Authors: Liu, P., Xie, X., Gao, L., Jin, J. Abstract: Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for SARS-CoV-2, and recombinant ACE2 decoys are being evaluated as new antiviral therapies. We designed and tested an ACE2-Fc fusion protein, which has the benefits of a long pharmacological half-life and the potential to facilitate immune clearance of the virus. Out of the concern that the intrinsic catalytic activity of ACE2 may unintentionally alter the balance of its hormonal substrates and cause adverse cardiovascular effects in treatment, we performed a mutagenesis screening for inactivating the enzyme. Three mutants, R273A, H378A and E402A, completely lost their enzymatic activity for either surrogate or physiological substrates. All of them remained capable of binding SARS-CoV-2 and could suppress the transduction of a pseudotyped virus in cell culture. This study established new ACE2-Fc candidates as antiviral treatment for SARS-CoV-2 without potentially harmful side effects from ACE2 catalytic actions toward its vasoactive substrates. Copy rights belong to original authors. Visit the link for more info