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Updated: Oct 18, 2025

Isolation of Lipoprotein Particles from Chicken Egg Yolk for the Study of Bacterial Pathogen Fatty Acid Incorporation into Membrane Phospholipids
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Pharmacological inhibition of fatty acid synthesis blocks SARS-CoV-2 replication

Junjun Chu1, Changsheng Xing1, Yang Du1

  • 1Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Nature Metabolism
|September 28, 2021
PubMed

Insights

Cellular lipid synthesis fuels SARS-CoV-2 replication. Inhibiting fatty acid synthase with drugs like orlistat reduced viral load and improved survival in a mouse model, offering a potential COVID-19 treatment.

Area of Science:

  • Virology
  • Biochemistry
  • Pharmacology

Background:

  • COVID-19, caused by SARS-CoV-2, is a severe inflammatory respiratory disease with multi-organ damage.
  • Cellular lipid synthesis plays a crucial role in viral replication and presents a potential therapeutic target.

Purpose of the Study:

  • To identify host metabolic genes involved in SARS-CoV-2 replication.
  • To evaluate fatty acid synthase inhibitors as potential antiviral agents against SARS-CoV-2.

Main Methods:

  • Screening of a short-hairpin RNA library targeting metabolic genes.
  • In vitro testing of fatty acid synthase inhibitors, including orlistat, against SARS-CoV-2 variants.
  • In vivo efficacy study using a K18-hACE2 mouse model of SARS-CoV-2 infection.

Main Results:

  • ACACA and FASN, key genes in lipid synthesis, were identified as crucial for SARS-CoV-2 replication.
  • Orlistat, an FDA-approved fatty acid synthase inhibitor, demonstrated in vitro inhibition of SARS-CoV-2 and its variants.
  • Orlistat treatment in mice reduced viral load, lung pathology, and increased survival rates.

Conclusions:

  • Inhibitors of fatty acid synthase are promising drug candidates for COVID-19 treatment by targeting viral replication.
  • Repurposing fatty acid synthase inhibitors warrants further investigation in clinical trials for severe COVID-19.

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