Activation of Peroxiredoxin 1 by Fluvastatin Effectively Protects from Inflammation and SARS-CoV-2

Excessive reactive oxygen species (ROS) is highly involved in inflammation and the pathogenesis of infectious diseases. As a potent scavenger of ROS, peroxiredoxin 1 (PRDX1) is a promising therapeutic target for treating ROS-related diseases, however, its agonist has not been identified yet. Here we report the identification of the cholesterol-lowering drug Fluvastatin as an effective and selective agonist of PRDX1. As revealed by the high-resolution complex crystal structure, Fluvastatin binds to a pocket adjacent to the active site of PRDX1. Activation of PRDX1 with Fluvastatin decreased the intracellular ROS and proinflammatory responses in cultured cells. Interestingly, Fluvastatin treatment inhibited SARS-CoV-2 infection and replication in Vero E6 cells. Our findings suggest that activation of PRDX1 is a sound strategy for combating severe inflammatory diseases and viral infections such as SARS-CoV-2. In this regard, Fluvastatin remains to be a promising drug, particularly in SARS-CoV-2 patients with cardiovascular diseases.