MEDS433

MEDS433 is a novel small molecule inhibitor of human dihydroorotate dehydrogenase (hDHODH), an essential enzyme in the de novo pyrimidine biosynthesis pathway. By blocking hDHODH activity, MEDS433 deprives viruses and cancer cells of pyrimidines, thereby inhibiting replication. It exhibits broad-spectrum antiviral activity against influenza A and B viruses, human coronaviruses including SARS-CoV-2, herpes simplex viruses, and respiratory syncytial viruses, all at low nanomolar concentrations. MEDS433 also shows preclinical efficacy in models of myeloid leukemia and may be useful in treating various neoplastic and hematologic disorders. Its antiviral effects can be reversed by supplementation with exogenous uridine or orotate, confirming DHODH as its molecular target. MEDS433 was developed on the scaffold of brequinar, and is under preclinical investigation by the University of Turin as a potential host-targeted antiviral and anticancer therapeutic.[1][2][3][4][5][9]