New potent EV-A71 antivirals targeting capsid Roux, H. /Touret, Franck Coluccia, A. Khoumeri, O. Di Giorgio, C. Majdi, C. Sciò, P. Silvestri, R. Vanelle, P. Roche, M. 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. 2024 text https://www.documentation.ird.fr/hor/fdi:010093043 fdi:010093043 Roux H., Touret Franck, Coluccia A., Khoumeri O., Di Giorgio C., Majdi C., Sciò P., Silvestri R., Vanelle P., Roche M.. New potent EV-A71 antivirals targeting capsid. 2024, 276, 116658 [18 ] EN