Abstract/Summary

The renin–angiotensin system (RAS) is a key regulator of blood pressure and hypertension. An-giotensin converting enzyme 2 (ACE2) and angiotensin converting enzyme I (ACE) are two main components of the RAS that play a major role in blood pressure homeostasis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 as a receptor to enter the cells. Despite some controversies, numerous studies have reported a significant association be-tween the use of ACE inhibitors, and reduced risk of COVID-19. In our previous studies, we pro-duced and identified peptide sequences present in whey hydrolysates exhibiting high ACE in-hibitory activity. Therefore, the aim of this work is to obtain an improved understanding of the function of these natural peptides as RAS inhibitors and investigate their potential therapeutic role in the COVID-19 pandemic. The molecular interactions between peptides IPP, LIVTQ, IIAE, LVYPFP, and human ACE2 were assessed employing a molecular docking approach. The results show that natural whey-derived peptides have a dual inhibitory action against both ACE and ACE2. This dual activity distinguishes these ACE inhibitory peptides from synthetic drugs, such as Captopril and Lisinopril that were not shown to inhibit ACE2 activity, and may represent a potential strategy in the treatment of COVID-19.