A new approach to the use of angiotensin-converting enzymes 1 and 2 as a therapeutic agent

• Grant number: 23/03497-5
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2023
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Regina Affonso
• Grantee: Regina Affonso
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The main public health problems that affect the world today are cardiovascular and pulmonary diseases (WHO / 2020), which have in common the renin angiotensin system (RAS). This system acts by endocrine, paracrine and intracrine pathways, with emphasis on its function in the regulation of blood pressure and the balance of salts in the human body. In this system, the angiotensin-converting enzyme 1 (ACE1) participates in the control of blood pressure, in brain protection by the cleavage of beta amyloid bodies, cell proliferation, hematopoietic stem cells formation, among others. Lung diseases worsened markedly with COVID-19, a pandemic caused by the SARS-CoV-2 virus. One of the well-documented cell invasion strategies for this virus is through the angiotensin-converting enzyme 2 (ACE2), which also plays a role in RAS. The use of peptides for diagnosis and therapy is a reality in wide expansion and ACE1 and ACE2 can be interesting tools for the solution of these dysfunctions. Obtaining the peptides that correspond to the ACE1 catalytic sites, N- and C-domains, will enable greater assertiveness in obtaining and characterizing new hypertensive drugs, as well as in the evaluation of the hydrolysis capacity of substrates such as beta amyloid. The synthesis of the peptide that corresponds to the ACE2 binding region with SARS-CoV-2, can be used to inhibit the entry of this virus into cells and to detect it in samples of human secretion and surfaces. This approach to the synthesis of the catalytic sites and COVID-19 inhibitory peptide is unique, not yet described in the literature and already in progress in our laboratory. The excellence of these peptides is that, a priori, they will not cause rejection and may have minimal side effects, since they are parts of human enzymes. (AU)