The human surface-expressed angiotension-converting enzyme 2 (ACE2) receptor has been identified as a functional receptor to mediate in vitro and in vivo cell-entry of SARS-CoV-2 – the etiological virus underpinning the current COVID-19 pandemic. SARS-CoV-2 infection has also been shown to lead to a substantial decrease in surface expression of ACE2 receptor, resulting in a dominant ACE activity and consequently shifting the renin-angiotensin (RA) signalling axis toward a phenotype of vascular hypertension, inflammation and fibrosis. Ultimately, such a shift has a high tendency to trigger acute respiratory distress syndrome (ARDS) – one of the most devastating forms of acute lung failure. In particular, patients with pre-existing cardiovascular disease and the aged population have a 5-8 fold increased risk of death from COVID-19 due to ARDS, a group which account for >80% COVID-19 death.
To address these ongoing issues, we aim to develop high-affinity ACE2 variants which are capable of scavenging SARS-CoV-2 virus effectively in vivo whilst offering lung- and cardiovascular-protective effects to equivalent levels with respect to current recombinant ACE2 therapeutics.
Aim 1: Developing high-affinity ACE2 peptide fragments against SARS-COV-2 infection.
Aim 2: Investigating the binding affinity against SARS-COV-2 Spike protein using FACS.