A deeper investigation in the lipid role for virus infections: phosphoinositides and oxylipins

• Grant number: 23/08462-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: October 01, 2023
• End date: September 30, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Sayuri Miyamoto
• Grantee: Rosangela Silva Santos
• Supervisor: Britta Bruegger
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Heidelberg University, Germany
• Associated to the scholarship: 21/13711-9 - Aging-mediated lipid alterations in SARS-CoV-2 infection, BP.DD

Abstract

Respiratory infections caused by coronavirus were responsible for three outbreaks in 2003, 2012 and 2019. Covid-19 caused by Sars-Cov-2 was responsible for more than 6.9 million deaths. The understanding of virus metabolism in the organism could lead to the production of new drugs that prevent viral contamination at pandemic levels. Lipid metabolism have been showing high relevance for viral infections. A significant study conducted by Bartenschlager and the Brügger group (Heidelberg, Germany) showed that phosphatidic acids are necessary for Sars-Cov-2 and hepatitis C replication organelle production. Additionally, recent results by our group showed a higher amount of phosphatidilinositols (PI) in Sars-Cov-2 infected cells compared with mock control. Similar alterations were observed in vivo. Two PI species (PI 16:0/18:2 and PI 18:1/20:4) were also higher in the lung of Sars-Cov-2 infected Syrian hamsters at 3 days post infection (dpi). These results suggest a strong correlation between phosphatidylinositol species and its precursors: the phosphatidic acids during viral infection. Another important feature of Covid-19 is the elevated levels of oxylipins, especially prostaglandins, in patients and Syrian hamster lungs. However, this trend was not observed in a traditional cell culture model. This project aims to establish the relationship between phosphatidylinositol and its products: the phosphoinositides for the replication organelle production, and to evaluate the use of patients derived lung organoids as a most suitable in vitro model. Phosphatidylinositol and phosphoinositide analyses will be analyzed by liquid chromatography coupled to mass spectrometry. The characterization of phosphoinositides (PtIns) will be performed with a previous phosphate methylation step as previous described by the Brügger group (Heidelberg, Germany) in the quantification of monodolichyl phosphates. Oxylipin analysis will be carried in the optimal conditions established by the Miyamoto group (Sao Paulo, Brazil). We expect to identify specific phosphoinositides that could be targeted to diminish viral replication and contribute with an in vitro model that will improve translational research in near future. (AU)