PT - JOURNAL ARTICLE AU - Suelen da Silva Gomes Dias AU - Vinicius Cardoso Soares AU - André C. Ferreira AU - Carolina Q. Sacramento AU - Natalia Fintelman-Rodrigues AU - Jairo R. Temerozo AU - Lívia Teixeira AU - Ester Barreto AU - Mayara Mattos AU - Caroline S. de Freitas AU - Isaclaudia G. Azevedo-Quintanilha AU - Pedro Paulo A. Manso AU - Eugenio D. Hottz AU - Camila R. R. Pão AU - Dumith C. Bou-Habib AU - Fernando A. Bozza AU - Thiago M. L. Souza AU - Patrícia T. Bozza TI - Lipid droplets fuels SARS-CoV-2 replication and inflammatory response AID - 10.1101/2020.08.22.262733 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.08.22.262733 4099 - http://biorxiv.org/content/early/2020/08/23/2020.08.22.262733.short 4100 - http://biorxiv.org/content/early/2020/08/23/2020.08.22.262733.full AB - 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 demonstrate 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, as CD36, SREBP-1, PPARγ and DGAT-1 in human 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. The 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.Competing Interest StatementThe authors have declared no competing interest.