Table 1. Inhibition of SAH Hydrolase and the Replication of Several +RNA Viruses by All Final Nucleoside Analogues 2a–j and 3a–ca,b,c,d.
| MERS-CoV |
SARS-CoV |
ZIKV |
CHIKV |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| compound no. | SAH hydrolase IC50 (μM) | EC50 (μM) | CC50 (μM) | SI | EC50 (μM) | CC50 (μM) | SI | EC50 (μM) | CC50 (μM) | SI | EC50 (μM) | CC50 (μM) | SI |
| 1 | 1.32 | >50 | 2 | >50 | >5 | 0.64 | 2.4 | 3.8 | 0.8 | 6.3 | 7.9 | ||
| 2a | 0.37 | 0.20 | 0.60 | 3 | ND | ND | ND | ND | >100 | >100 | |||
| 2b | 9.70 | ND | ND | ND | ND | 2.54 | 3.97 | 1.56 | 0.53 | 1.32 | 2.49 | ||
| 2c | 1.06 | 0.2 | 3.2 | 16 | 0.5 | 5.9 | 11.8 | 0.26 | >2.5 | >9.6 | 0.13 | >1.25 | >9.6 |
| 2d | 4.39 | >50 | >50 | >100 | >100 | >100 | >100 | >100 | >100 | ||||
| 2e | 0.76 | >50 | 12.5 | >100 | >100 | >100 | >100 | >100 | >100 | ||||
| 2f | >100 | >100 | >100 | >100 | >100 | >100 | >100 | >100 | >100 | ||||
| 2g | >100 | >100 | >100 | >100 | >100 | >100 | >100 | >100 | >100 | ||||
| 2h | >100 | >50 | >50 | >100 | >100 | >100 | >100 | >100 | >100 | ||||
| 2i | >100 | >100 | >100 | >100 | >100 | >100 | >100 | >100 | >100 | ||||
| 2j | >100 | >50 | >50 | >100 | >100 | >100 | >100 | >100 | >100 | ||||
| 3a | >100 | 9.3 | >50 | 6.8 | >25 | >3.7 | 1.75 | >25 | >14.3 | 1.95 | >12.5 | >6.4 | |
| 3b | >100 | >50 | >50 | >100 | >100 | >100 | >100 | >100 | >100 | ||||
| 3c | >100 | >50 | >50 | >100 | >100 | >100 | >100 | >100 | >100 | ||||
a
ND: not determined; SI = CC50/EC50.
b
EC50: effective concentration to inhibit the replication of the virus by 50%.
c
CC50: cytotoxic concentration to inhibit the replication of normal cells by 50%.
d
EC50 > 100 indicates that no antiviral activity was observed at the highest concentration tested because either there was no protection or the compound was toxic.