Perspectives: potential therapeutic approach with inhalation of ACE2-derived peptides for SARS-CoV-2 infection.

Objective: ACE2 is crucially involved in the infection sustained by SARS-CoV-2, as it allows the entry of the virus into target cells while counteracting local inflammation, oxidative stress, and fibrosis. In this narrative review, we aim to discuss the usefulness of ACE2-derived peptides in the infection sustained by SARS-CoV-2.

Methods: A total of 49 papers pertinent to the purpose of the review were selected from the PubMed and Google Scholar databases. Clinical trials registered at ClinicalTrials.gov and dealing with the use of ACE2-derived medications in COVID-19 were also searched and discussed.

Results: Preclinical and clinical evidence shows that drugs mimicking or potentiating the effects of ACE2 may reduce the viral load and dampen the inflammatory and fibrotic pathways leading to respiratory distress. ACE2-derived therapeutic peptides may have a better pharmacokinetic and pharmacodynamic profile than other ACE2-based medications. They could be easily screened through peptide libraries and chemically modified in order to ameliorate the pharmacological properties. Furthermore, their local administration via an intranasal delivery or inhalation may reduce the risk of systemic side effects, thus conferring a good safety profile.

Conclusion: ACE2-derived peptides may play a dual beneficial role in COVID-19, by either preventing virus spread or inhibiting the secretion of pro-inflammatory mediators in airways. Viral, host, and environmental factors may affect the effectiveness of this therapeutic approach to a various extent and represent therefore a matter of investigation for future studies.