The new generation hDHODH inhibitor MEDS433 hinders the in vitro replication of SARS-CoV-2
A. Calistri, A. Luganini, V. Conciatori, C. Del Vecchio, S. Sainas, D. Boschi, M. L. Lolli, G. Gribaudo, C. Parolin
Abstract
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.
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