Human recombinant ace2-fc mutants that decouple anti-sars-cov-2 activity from cardiovascular effects
AssigneeNorthwestern University
InventorsJing Jin, Pan Liu
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Abstract
Disclosed are compounds, compositions, and methods for treating and/or preventing infection by viruses that utilize the angiotensin converting enzyme 2 (ACE2) as a cellular receptor such as sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Particularly disclosed are recombinant ACE2-Fc fusion proteins and ACE2 variants that exhibit anti-SARS-CoV-2 binding activity and decouple anti-SARS-CoV-2 activity from side effects such as cardiovascular effects, where the fusion proteins and variants exhibit reduced ACE2 enzymatic activity.
Claims37
A fusion protein comprising:
- (i) at least a portion of the ectodomain of human angiotensin converting enzyme 2 (ACE2) fused directly or via a linking sequence to (ii) at least a portion of the constant region of a human antibody;
- wherein the fusion protein binds to the spike protein of sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the fusion protein comprises one or more mutations in ACE2 that result in reduced peptidase activity.
A human angiotensin converting enzyme 2 (ACE2) protein comprising one or more mutations selected from a mutation at position E145, R273, H345, P346, D368, H374, H378, E402, H505, or combinations thereof.
Dependencies are inferred from the claim text.