Study of the mechanisms involved in the modulation of the renin-angiotensin System in the three-dimensional bronchioles from a 3D human co-culture infected by SARS-CoV-2 to produce inflammatory mediators

• Grant number: 20/10711-5
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2021
• End date: October 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Sandra Helena Penha de Oliveira
• Grantee: Sandra Helena Penha de Oliveira
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Associated researchers: Carlos Ferreira dos Santos ; Celio Lopes Silva ; Fábio Bombarda

Abstract

An outbreak of new coronavirus-related pneumonia was identified in December 2019, and has expanded rapidly, with cases now confirmed in more than 211 countries or more areas. This constant transmission of a new SARS-CoV-2 and its ability to spread from human to human led scientists to develop new approaches to the treatment of COVID-19. One of the main targets of this virus is to drastically alter the host's immune system, causing an exacerbated release of cytokines and chemokines leading to changes in the immune response and damaging the airways. The input receptor for this SARS-CoV-2 is that of the angiotensin-converting enzyme 2 (ACE2), involved in the renin-angiotensin system (RAS) and the main protein bound by the virus to this receptor is protein S. Several drugs are being used for reducing the symptoms of this disease and its side effects, however, none of them have been effective in reducing the damage to the host more quickly. Thus, the objective of the present study will be to evaluate the mechanisms involved in RAS modulation by three-dimensional bronchiole co-culture 3D infected by SARS-CoV-2 for production of inflammatory mediators in the presence of RAS axis inhibitors and inhibitors of protein S of SARS-CoV-2. The discovery of new mechanisms to modulate the immune response could be a new pharmacological tool to contain the infection and could be of great advancement for the treatment of inflammatory manifestations of this disease that affects the world population. (AU)