Targeting the fatty acid metabolism pathway represents a promising antiviral strategy against diverse viral infections.

Fatty acids (FAs) are important regulators of immune responses and innate defense mechanisms, which can be hijacked by viruses to impair the host innate immune response and establish persistent infections. Interestingly, FAs are also known for their broad-spectrum antiviral properties. Yet the precise mechanisms by which FAs regulate viral replication remain incompletely understood. Emerging evidence now suggests that virus infection regulates the expression of fatty acid metabolic enzymes, driving lipid remodeling that supports multiple stages of the viral life cycle. Additionally, FAs can enhance viral gene expression, protein stability, and the formation of replication complexes. Conversely, host cells also require reprogramming FAs biosynthesis to resist viral infections. Intriguingly, some fatty acid ratios may serve as a prognostic indicator after virus infection. Therefore, limiting FAs synthesis will impair infectivity of viruses, which could be an effective antiviral strategy. This review summarizes the impact of FA synthesis and elongation on the virus lifecycle, focusing on the underlying mechanisms of how viruses exploit host FAs and their downstream product lipid droplets to facilitate viral replication. We have also provided valuable insights on the development and utilization of antiviral drugs by manipulating FA metabolism.