Table 2. Anti-SARS-CoV-2 RdRp/ExoN Activities (along with Respective Ratios) of the Target Repurposed Drugs Riboprine, Forodesine, Nelarabine, Tecadenoson, Maribavir, and Vidarabine (Using Both Remdesivir and Molnupiravir as the Positive Control/Reference Drugs and DMSO as the Negative Control/Placebo Drug) and the TP Nucleotides Forodesine-TP and Riboprine-TP (Using Both GS-443902 and NHC-TP as the Positive Control/Reference Drugs and DMSO as the Negative Control/Placebo Drug), respectively, in HEK293T Cells, Expressed as EC50 Values in μM (Please Note That, in This Table, nsp12 Refers to the nsp12/7/8 Complex, nsp14 Refers to the nsp14/10 Complex, and nsp14mutant Refers to the nsp14mutant/10 Complex).
| inhibition of SARS-CoV-2 RdRp in vitro (EC50 in μM)a |
respective
ratios of EC50 |
|||||
|---|---|---|---|---|---|---|
| classification | compound name | Nsp12 | nsp12 + nsp14 | nsp12 + nsp14mutant | (nsp12 + nsp14)/nsp12 | (nsp12 + nsp14mutant)/nsp12 |
| repurposed NAs | riboprine | 0.18 ± 0.02 | 0.28 ± 0.03 | 0.23 ± 0.02 | 1.56 | 1.28 |
| forodesine | 0.20 ± 0.03 | 0.31 ± 0.03 | 0.25 ± 0.03 | 1.55 | 1.25 | |
| nelarabine | 0.65 ± 0.04 | 1.22 ± 0.06 | 1.09 ± 0.05 | 1.88 | 1.68 | |
| tecadenoson | 0.99 ± 0.06 | 1.38 ± 0.06 | 1.29 ± 0.04 | 1.39 | 1.30 | |
| maribavir | 1.07 ± 0.05 | 1.89 ± 0.07 | 1.45 ± 0.07 | 1.77 | 1.36 | |
| vidarabine | 1.08 ± 0.06 | 2.02 ± 0.08 | 1.47 ± 0.07 | 1.87 | 1.36 | |
| reference drugs | remdesivir | 1.12 ± 0.06 | 2.11 ± 0.09 | 1.55 ± 0.07 | 1.88 | 1.38 |
| molnupiravir | 0.24 ± 0.03 | 0.45 ± 0.05 | 0.33 ± 0.04 | 1.88 | 1.38 | |
| placebo solvent | DMSO | >100 | >100 | >100 | N.A.b | N.A. |
| TP nucleotide forms of the top-ranked repurposed NAs | forodesine-TP | 0.16 ± 0.02 | 0.25 ± 0.04 | 0.20 ± 0.02 | 1.56 | 1.25 |
| riboprine-TP | 0.17 ± 0.02 | 0.27 ± 0.03 | 0.21 ± 0.03 | 1.59 | 1.24 | |
| active TP metabolites of the reference drugs | GS-443902 | 1.05 ± 0.05 | 2.01 ± 0.09 | 1.51 ± 0.06 | 1.91 | 1.44 |
| NHC-TP | 0.23 ± 0.03 | 0.42 ± 0.05 | 0.31 ± 0.03 | 1.83 | 1.35 | |
a
EC50 or 50% effective concentration is the concentration of the tested compound that is required for 50% reduction in the COVID-19 polymerase (SARS-CoV-2 RdRp) activity in vitro. EC50 is expressed in μM.
b
N.A. means not available (i.e., it was not determined).