The new generation hDHODH inhibitor MEDS433 hinders the in vitro replication of SARS-CoV-2

Identification and development of effective drugs active against SARS-CoV-2 are urgently needed. Here, we report on the anti-SARS-CoV-2 activity of MEDS433, a novel inhibitor of human dihydroorotate dehydrogenase (hDHODH), a key cellular enzyme of the de novo pyrimidines biosynthesis. MEDS433 inhibits in vitro virus replication in the low nanomolar range, and through a mechanism that stems from its ability to block hDHODH activity. MEDS433 thus represents an attractive candidate to develop novel anti-SARS-CoV-2 agents.