Lipid droplets fuels SARS-CoV-2 replication and inflammatory response

Gomes Dias, S. S.; Cardoso, V. S.; Ferreira, A. C.; Sacramento, C. Q.; Fintelman-Rodrigues, N.; Temerozo, J. R.; Teixeira, L.; Barreto, E. A.; Mattos, M.; de Freitas, C. S.; Azevedo-Quintanilha, I.; Manso, P. P. A.; Hottz, E. D.; Pao, C. R. R.; Bou-Habib, D. C.; Bozza, F. A.; Souza, T. M. L.; Bozza, P. T.

doi:10.1101/2020.08.22.262733

bioRxiv · 10.1101/2020.08.22.262733

Lipid droplets fuels SARS-CoV-2 replication and inflammatory response

Gomes Dias, S. S.·Cardoso, V. S.·Ferreira, A. C.·Sacramento, C. Q.·Fintelman-Rodrigues, N.·Temerozo, J. R.·Teixeira, L.·Barreto, E. A.·Mattos, M.·de Freitas, C. S.·Azevedo-Quintanilha, I.·Manso, P. P. A.·Hottz, E. D.·Pao, C. R. R.·Bou-Habib, D. C.·Bozza, F. A.·Souza, T. M. L.·Bozza, P. T.

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Abstract

Viruses are obligate intracellular parasites that make use of the host metabolic machineries to meet their biosynthetic needs, identifying the host pathways essential for the virus replication may lead to potential targets for therapeutic intervention. The mechanisms and pathways explored by SARS-CoV-2 to support its replication within host cells are not fully known. Lipid droplets (LD) are organelles with major functions in lipid metabolism and energy homeostasis, and have multiple roles in infections and inflammation. Here we described that monocytes from COVID-19 patients have an increased LD accumulation compared to SARS-CoV-2 negative donors. In vitro, SARS-CoV-2 infection modulates pathways of lipid synthesis and uptake, including CD36, SREBP-1, PPAR{gamma} and DGAT-1 in monocytes and triggered LD formation in different human cells. LDs were found in close apposition with SARS-CoV-2 proteins and double-stranded (ds)-RNA in infected cells. Pharmacological modulation of LD formation by inhibition of DGAT-1 with A922500 significantly inhibited SARS-CoV-2 replication as well as reduced production of pro-inflammatory mediators. Taken together, we demonstrate the essential role of lipid metabolic reprograming and LD formation in SARS-CoV-2 replication and pathogenesis, opening new opportunities for therapeutic strategies to COVID-19.

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Gomes Dias, S. S., Cardoso, V. S., Ferreira, A. C., Sacramento, C. Q., Fintelman-Rodrigues, N., Temerozo, J. R., Teixeira, L., Barreto, E. A., Mattos, M., de Freitas, C. S., Azevedo-Quintanilha, I., Manso, P. P. A., Hottz, E. D., Pao, C. R. R., Bou-Habib, D. C., Bozza, F. A., Souza, T. M. L., Bozza, P. T.. 2020-08-23. Lipid droplets fuels SARS-CoV-2 replication and inflammatory response. https://doi.org/10.1101/2020.08.22.262733

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