Natural Product Bruceine A from <i>Brucea javanica</i><i>(L.) Merr.</i> 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 <i>Brucea javanica</i> <i>(L.) Merr.</i> which inhibited vesicular stomatitis virus (VSV) infection <i>in vitro</i>. Mechanistically, BA blocked viral adsorption and internalization, facilitating antiviral effects through lysosome-mediated degradation of LDLR. Genetic knockdown of <i>Ldlr</i> 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.