Assessment of the role of the AT1 receptor in the bronchotracheal inflammatory process induced by the SARS-CoV-2 Spike protein in asthmatic mice.

• Grant number: 25/00117-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Sandra Helena Penha de Oliveira
• Grantee: Thales Polizel Guidotti Ribeiro
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

SARS-CoV-2 emerged in 2019, causing a global pandemic. One of its protein components is the Spike (S) protein, which is responsible for the viral invasion of the host by binding to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell surface. The binding of the virus induces a reduction in the expression of ACE2, negatively regulating its cycle and increasing the expression of ACE, causing a cytokine storm mainly in the lungs. Asthma is one of the most common chronic diseases in the world. It is characterized by chronic airway inflammation, which various factors, including pathogens, can aggravate. Studies have found that asthmatic patients had a lower rate of SARS-CoV-2 infection. One of the reasons for the low infection rate is due to the low expression of ACE2, making it more difficult for SARS-COV-2 to bind and replicate; however, if infected, they cause a deregulation of the ACE and ACE2 pathway. Knowing that ACE2 is a protector of severe acute lung failure, the virus would cause dysregulation of this pathway, making COVID-19 more lethal. The use of Ang II (AT1) receptor antagonist drugs could positively regulate ACE2; however, with increased ACE2 expression, there would be an opportunity for the virus to replicate again. Therefore, this project aims to evaluate the role of the AT1 receptor in lung inflammation in asthmatic mice infected with the Spike protein. Evaluating the role of a drug involved in modulating the renin-angiotensin system could be an effective tool for future studies related to asthma and COVID-19.