Transferrin Receptor as a Target for Regulation of Ferroptosis and Some Viral Infections

This review is devoted to molecular mechanisms of ferroptosis, a type of programmed cell death dependent on lipid peroxidation and limited by iron influx, mediated by the transferrin receptor (TfR1 or CD71). In addition to the iron-saturated transferrin, ligands of transferrin receptor also include its homologues lactoferrin and melanotransferrin, as well as heavy-chain ferritin and heme complex with human serum albumin. Activation of ferroptosis, including by increasing the labile pool of iron in tumor cells, is considered a promising strategy for combating cancer. However, a number of pathogenic human viruses, including influenza virus, SARS-CoV-2 coronavirus, and rabies virus, use binding with TfR1 to infect cells and affect ferroptosis. The review summarizes information on natural and synthetic TfR1 regulators, including the mechanisms of their influence on the development of ferroptosis and the prospects for their use as antiviral agents.