Study of the ability of drugs to inhibit the NSP3-mediated lung proinflammatory response of SARS-CoV-2 through modulation of the STAT3 pathway

• Grant number: 23/02034-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2023
• End date: February 29, 2024
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Rodrigo Esaki Tamura
• Grantee: João Gabriel Jaze Alves
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated research grant: 19/15619-2 - Development of high capacity adenoviral system expressing antitumoral genes, AP.JP

Abstract

The recent COVID-19 epidemic is one of the greatest public health challenges of this century. The disease caused social and economic disruption across the world. The ease of transmission of SARS-CoV-2 and its progression to clinical conditions, which in many cases require hospitalization, require redirecting efforts to combat this virus. New or old drugs should be evaluated for activity against this coronavirus. The drugs Nifuroxazide and Metformin have been used for decades and have recently been repositioned for other diseases, such as cancer, because they are potent STAT3 inhibitors, which are constitutively activated in different forms of cancer. SARS-CoV, which caused the 2002-2003 coronavirus outbreak, expresses the protein, NSP3, leads to the activation of STAT3, which in turn can lead to the activation of TGF-²1, and can promote lung fibrosis, in addition to participate in the exacerbated activation of the immune system. In this project, we intend to evaluate the ability of these drugs to inhibit STAT3 in different cell lines that overexpress domains of the NSP3 protein and to evaluate the expression of genes related to pulmonary fibrosis and pro-inflammatory cytokines.