ABSTRACT
The renin-angiotensin system (RAS) is a key regulator of blood pressure and hypertension. Angiotensin-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 cells. Despite some controversies, numerous studies have reported a significant association between the use of ACE inhibitors and reduced risk of COVID-19. In our previous studies, we produced and identified peptide sequences present in whey hydrolysates exhibiting high ACE inhibitory 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 by 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 which were not shown to inhibit ACE2 activity, and may represent a potential strategy in the treatment of COVID-19.
Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19 Drug Treatment , Peptides/chemistry , Peptides/pharmacology , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme Inhibitors/chemistry , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , Peptides/metabolism , Peptidyl-Dipeptidase A/chemistry , Renin-Angiotensin System/drug effects , Whey Proteins/chemistryABSTRACT
The COVID-19, an acute respiratory syndrome caused by SARS-CoV2 is a major catastrophic event of the twenty first century. Relentless efforts for the development of effective pharmaco-therapeutics are in progress but the respite is the development of effective vaccines. However, monotherapy might not always exhibit complete efficacy and may culminate in the rapid evolution of drug-resistant viral strains. Hence, simultaneous modulation of multiple druggable targets not only enhances therapeutic efficacy but also quell the prospects of mutant viruses. Currently, milk peptides have bloomed beyond just being a quintessential part of nutrition to prominent therapeutic implications in human health and diseases. Hence, we have focused on colostrum/milk peptides as they have already been acknowledged for their high potency, target specificity with significantly low or no side effects and bio-toleration. The results presented provide a conceptual strategy for the rational designing of prospective multitargeted peptide inhibitors for SARS-CoV2.