Natural Product Bruceine A from Brucea javanica(L.) Merr. as a Potential LDLR Inhibitor That Facilitates Antiviral Effect

Low-density lipoprotein receptor (LDLR), which serves as one of the most major entry receptors for many viruses in both human and mouse cells, plays a vital role in virus infection. However, there are no effective small molecules available to inhibit LDLR expression and exhibit antiviral effects. Here, we screened Bruceine A (BA), a natural product derived from the major constituents in Brucea javanica(L.) Merr. which inhibited vesicular stomatitis virus (VSV) infection in vitro. Mechanistically, BA blocked viral adsorption and internalization, facilitating antiviral effects through lysosome-mediated degradation of LDLR. Genetic knockdown of Ldlr exhibited strong antiviral effects. To the best of our knowledge, BA is the first LDLR-selective inhibitor, and our findings reveal that BA may serve as a potent and broad-spectrum virus entry inhibitor based on LDLR entry receptor.