Development of a novel angiotensin converting enzyme 2 stimulator with broad implications in SARS-CoV2 and type 1 diabetes

Res Sq [Preprint]. 2023 Apr 5:rs.3.rs-2642181. doi: 10.21203/rs.3.rs-2642181/v1.

Abstract

Angiotensin-converting enzyme 2 (ACE2) is protective in cardiovascular disease, lung injury and diabetes yet paradoxically underlies our susceptibility to SARs-CoV2 infection and the fatal heart and lung disease it can induce. Furthermore, diabetic patients have chronic, systemic inflammation and altered ACE2 expression resulting in increased risk of severe COVID-19 and the associated mortality. A drug that could increase ACE2 activity and inhibit cellular uptake of severe acute respiratory syndrome coronavirus 2 (SARs-CoV2), thus decrease infection, would be of high relevance to cardiovascular disease, diabetes and SARs-CoV2 infection. While the need for such a drug lead was highlighted over a decade ago receiving over 600 citations,1 to date, no such drugs are available.2 Here, we report the development of a novel ACE2 stimulator, designated '2A'(international PCT filed), which is a 10 amino acid peptide derived from a snake venom, and demonstrate its in vitro and in vivo efficacy against SARs-CoV2 infection and associated lung inflammation. Peptide 2A also provides remarkable protection against glycaemic dysregulation, weight loss and disease severity in a mouse model of type 1 diabetes. No untoward effects of 2A were observed in these pre-clinical models suggesting its strong clinical translation potential.

Publication types

  • Preprint

Grants and funding

National Foundation for Medical Research and Innovation Grant (SK, NWR) National Institutes of Health/National Institute of Aging (NIH, USA; 1R03AG054950-01A1) (SK, NWR) Start-up funds awarded by the Faculty of Medicine, The University of Queensland (NWR) Seed funding awarded by the Faculty of Medicine and Faculty of Health and Behavioural Science, The University of Queensland (NWR) National Health and Medical Research Council of Australia grant awarded (TMW, RJC)