Alpha-ketoamides as broad-spectrum inhibitors of coronavirus and enterovirus replication

Linlin Zhang; Daizong Lin; Yuri Kusov; Yong Nian; Qingjun Ma; Jiang Wang; Albrecht von Brunn; Pieter Leyssen; Kristina Lanko; Johan Neyts; Adriaan de Wilde; Eric J. Snijder; Hong Liu; Rolf Hilgenfeld

The EC50 of 11n was >10 µM against the EV-A71 and CVB3 replicons, and even in the SARS-CoV replicon, the activity of 11n was relatively weak (EC50 = 7.0 µM; Table 2 ). In agreement with the replicon data, 11n proved inactive against EV-A71 in RD cells and showed limited activity against HRV2 or HRV14 in HeLa Rh cells (Table 3) . Only the comparatively good activity (EC50 = 4.4 µM) against EV-D68 in HeLa Rh cells was unexpected. The activity of 11n against HCoV 229E in Huh7 cells was good (EC50 = 0.6 µM), and against MERS-CoV in Huh7 cells, it was excellent, with EC50 = 0.0048 µM, while in Vero cells, the EC50 against MERS-CoV was as high as 9.2 µM. Similarly, the EC50 against SARS-CoV in Vero cells was 14.2 µM (Table 3) .