Table 3. Anti-SARS-CoV-2/Anti-COVID-19 Activities (along with Cytotoxicities) 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, against SARS-CoV-2 (Omicron Variant, B.1.1.529.1/BA.1 Sublineage) in Vero E6 Cells.
| inhibition of SARS-CoV-2 replication in vitro (anti-B.1.1.529.1/BA.1 bioactivities) (μM) |
||||||
|---|---|---|---|---|---|---|
| classification | compound name | CC50a (μM) | 100% CPE inhibitory concentration (CPEIC100)b | 50% reduction in infectious virus (EC50)c | 50% reduction in viral RNA copy (EC50)d | 90% reduction in infectious virus (EC90)e |
| repurposed NAs | riboprine | >100 | 1.08 ± 0.04 | 0.40 ± 0.02 | 0.42 ± 0.02 | 1.50 ± 0.06 |
| forodesine | >100 | 1.58 ± 0.07 | 0.65 ± 0.03 | 0.69 ± 0.04 | 2.02 ± 0.07 | |
| nelarabine | >100 | 4.12 ± 0.15 | 1.67 ± 0.08 | 1.76 ± 0.08 | 6.42 ± 0.19 | |
| tecadenoson | >100 | 7.65 ± 0.25 | 2.86 ± 0.11 | 2.93 ± 0.12 | 11.89 ± 0.31 | |
| maribavir | >100 | 7.99 ± 0.28 | 3.00 ± 0.13 | 3.14 ± 0.15 | 12.24 ± 0.33 | |
| vidarabine | >100 | 8.05 ± 0.29 | 3.21 ± 0.12 | 3.25 ± 0.11 | 12.65 ± 0.36 | |
| reference drugs | remdesivir | >100 | 5.90 ± 0.26 | 2.01 ± 0.09 | 2.08 ± 0.10 | 7.97 ± 0.35 |
| molnupiravir | >100 | 6.24 ± 0.31 | 2.60 ± 0.11 | 2.71 ± 0.11 | 9.16 ± 0.37 | |
| placebo solvent | DMSO | >100 | >100 | >100 | >100 | >100 |
| TP nucleotide forms of the top-ranked repurposed NAs | forodesine-TP | >100 | 1.02 ± 0.04 | 0.38 ± 0.02 | 0.41 ± 0.03 | 1.46 ± 0.06 |
| riboprine-TP | >100 | 1.06 ± 0.05 | 0.39 ± 0.03 | 0.43 ± 0.03 | 1.51 ± 0.07 | |
| active TP metabolites of the reference drugs | GS-443902 | >100 | 4.88 ± 0.22 | 1.70 ± 0.08 | 1.82 ± 0.08 | 6.45 ± 0.29 |
| NHC-TP | >100 | 5.03 ± 0.25 | 2.14 ± 0.10 | 2.30 ± 0.11 | 7.89 ± 0.31 | |
CC50 or 50% cytotoxic concentration is the concentration of the tested compound that kills half the cells in uninfected cell culture. CC50 was determined with serially diluted compounds in Vero E6 cells at 48 h postincubation using the CellTiter-Glo Luminescent Cell Viability Assay (Promega).
CPEIC100 or 100% CPE inhibitory concentration is the lowest concentration of the tested compound that causes 100% inhibition of the cytopathic effects (CPE) of SARS-CoV-2 B.1.1.529.1/BA.1 virus in Vero E6 cells under increasing concentrations of the tested compound at 48 h postinfection. Compounds were serially diluted from 100 μM concentration.
EC50 or 50% effective concentration is the concentration of the tested compound that is required for 50% reduction in infectious SARS-CoV-2 B.1.1.529.1/BA.1 virus particles in vitro. EC50 is determined by infectious virus yield in culture supernatant at 48 h postinfection (log10 TCID50/mL).
EC50 or 50% effective concentration is the concentration of the tested compound that is required for 50% reduction in SARS-CoV-2 B.1.1.529.1/BA.1 viral RNA copies in vitro. EC50 is determined by viral RNA copies number in culture supernatant at 48 h postinfection (log10 RNA copies/mL).
EC90 or 90% effective concentration is the concentration of the tested compound that is required for 90% reduction in infectious SARS-CoV-2 B.1.1.529.1/BA.1 virus particles in vitro. EC90 is determined by infectious virus yield in culture supernatant at 48 h postinfection (log10 TCID90/mL).