Horizon 1 1 17 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES European Journal of Medicinal Chemistry 116658 [18 ] 2024 fdi:010093043 ENG European Journal of Medicinal Chemistry 0223-5234 ISI:001286467500001 10.1016/j.ejmech.2024.116658 https://www.documentation.ird.fr/hor/fdi:010093043 https://www.documentation.ird.fr/intranet/publi/2025-02/010093043.pdf 276 Horizon (IRD) The enterovirus is a genus of single-stranded, highly diverse positive-sense RNA viruses, including Human Enterovirus A-D and Human Rhinovirus A-C species. They are responsible for numerous diseases and some infections can progress to life-threatening complications, particularly in children or immunocompromised patients. To date, there is no treatment against enteroviruses on the market, except for polioviruses (vaccine) and EV-A71 (vaccine in China). Following a decrease in enterovirus infections during and shortly after the (SARS-Cov2) lockdown, enterovirus outbreaks were once again detected, notably in young children. This reemergence highlights on the need to develop broad-spectrum treatment against enteroviruses. Over the last year, our research team has identified a new class of small-molecule inhibitors showing anti-EV activity. Targeting the well-known hydrophobic pocket in the viral capsid, these compounds show micromolar activity against EV-A71 and a high selectivity index (SI) (5h: EC50, MRC-5 = 0.57 ?M, CC50, MRC-5 >20 ?M, SI > 35; EC50, RD = 4.38 ?M, CC50, RD > 40 ?M, SI > 9; 6c: EC50, MRC-5 = 0.29 ?M, CC50, MRC-5 >20 ?M, SI > 69; EC50, RD = 1.66 ?M, CC50, RD > 40 ?M, SI > 24; Reference: Vapendavir EC50, MRC-5 = 0.36 ?M, CC50, MRC-5 > 20 ?M, EC50, RD = 0.53 ?M, CC50, RD > 40 ?M, SI > 63). The binding mode of these compounds in complex with enterovirus capsids was analyzed and showed a series of conserved interactions. Consequently, 6c and its derivatives are promising candidates for the treatment of enterovirus infections. 052 ; 050 UR190 / UR237