An albumin-angiotensin converting enzyme 2-based SARS-CoV-2 decoy with FcRn-driven half-life extension

• DOI: 10.1016/j.actbio.2022.09.048
• Publication Date: 2022-09-24T08:18:47Z
• Authors: Elisabeth Fuchs; Imke Rudnik-Jansen; Anders Dinesen; Denis Selnihhin; Ole Aalund Mandrup; Kader Thiam; Jørgen Kjems; Finn Skou Pedersen; Kenneth A. Howard
• Keywords: Angiotensin-converting enzyme 2; Neonatal Fc receptor; Coronavirus; Wild type

The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants and breakthrough infections despite available disease 2019 (COVID-19) vaccines calls for antiviral therapeutics. application soluble angiotensin converting enzyme (ACE2) as a SARS-CoV-2 decoy that reduces cell bound ACE2-mediated virus entry is limited by short plasma half-life. This work presents recombinant human albumin ACE2 genetic fusion (rHA-ACE2) to increase the half-life an FcRn-driven cellular recycling mechanism, investigated using wild type (WT) sequence engineered with null FcRn binding (NB). Binding rHA-ACE2 fusions spike protein subdomain 1 (S1) was demonstrated (WT-ACE2 KD = 32.8 nM NB-ACE2 31.7 nM) Bio-Layer Interferometry dose-dependent in vitro inhibition host infection pseudotyped viruses displaying surface (S) protein. FcRn-mediated translated five times greater WT-ACE2 (t½ β 13.5 h) than 2.8 humanised FcRn/albumin double transgenic mice. rHA-ACE2-based system exhibiting circulatory extension introduced this offers potential expand improve anti-COVID-19 anti-viral drug armoury. STATEMENT OF SIGNIFICANCE: COVID-19 pandemic has highlighted need rapid development efficient therapeutics combat lower morbidity mortality cases, people are unable receive vaccine. Here we report therapeutic (rHA-ACE2), can bind S decorated virus-like particles inhibit viral infection, exhibits extended vivo compared alone. Employing expected efficiently all they rely on endogenous and, therefore, constitutes versatile addition arsenal combatting COVID-19.