Table 1.
IC50 values of remdesivir, molnupiravir, and nirmatrelvir against SARS-CoV-2 variants.
| Drug |
Remdesivir |
Molnupiravirc |
Nirmatrelvir |
|||
|---|---|---|---|---|---|---|
| Viral strain | IC50; μΜa (95% CI) | Fold changeb | IC50; μΜ (95% CI) | Fold change | IC50; μΜ (95% CI) | Fold change |
| Reference (S) | 2.24 (1.83–2.64) | 11.08 (9.51–12.66) | 1.51 (1.34–1.79) | |||
| Alpha (B.1.1.7) | 1.75 (1.53–2.01) | 0.78 | 6.19 (5.23–7.33) | 0.56 | 1.02 (0.94–1.10) | 0.68 |
| Beta (B.1.351) | 1.84 (1.53–2.194) | 0.82 | 7.97 (6.26–10.03) | 0.72 | 0.98 (0.94–1.07) | 0.65 |
| Gamma (P.1) | 2.73 (2.47–3.03) | 1.22 | 11.62 (10.8–12.49) | 1.05 | 1.371 (1.31–1.42) | 0.91 |
| Delta (B.1.627.2) | 3.70 (3.44–3.98) | 1.65 | 12.96 (10.67–14.51) | 1.17 | 1.01 (0.97–1.06) | 0.67 |
| BA.1 | 1.42 (1.22–1.63) | 0.63 | 4.66 (4.10–5.22) | 0.42 | 1.11 (1.02–1.22) | 0.74 |
| BA.2.2 | 1.95 (1.81–2.1) | 0.87 | 4.63 (4.23–5.07) | 0.42 | 0.84 (0.76–0.93) | 0.56 |
| BA.2 | 2.77 (2.39–3.21) | 1.24 | 8.09 (7.19–9.1) | 0.42 | 2.07 (1.89–2.26) | 0.56 |
| BA.2.12.1 | 1.28 (1.15–1.42) | 0.57 | 9.67 (8.09–11.55) | 0.87 | 1.25 (1.05–1.54) | 0.83 |
| BA.2.3 | 1.07 (0.94–1.22) | 0.48 | 7.53 (6.57–8.60) | 0.68 | 2.11 (1.90–2.35) | 1.40 |
| BA.4.1.1 | 3.34 (3.23–3.47) | 1.49 | 9.19 (8.74–9.66) | 0.83 | 1.83 (1.72–1.95) | 1.21 |
| BA.5.2.1 | 1.91 (1.51–2.37) | 0.85 | 1.94 (1.64–2.23) | 0.18 | 0.51 (0.49–0.53) | 0.30 |
| BA.2.75 | 1.59 (1.38–1.84) | 0.71 | 7.31 (6.18–8.64) | 1.16 | 0.54 (0.52–0.56) | 0.34 |
| BA.4.6 | 1.82 (1.52–2.17) | 0.81 | 4.74 (2.91–7.26) | 0.43 | 0.92 (0.76–1.11) | 0.61 |
| BA.2.75.2 | 4.34 (4.04–4.65) | 1.94 | 2.92 (2.66–3.20) | 0.26 | 1.27 (1.2–1.36) | 0.84 |
| BF.7 | 2.45 (2.35–2.54) | 1.09 | 9.4 (9.01–9.81) | 0.85 | 1.32 (1.26–1.39) | 0.87 |
| BQ.1.5 | 3.04 (2.59–3.57) | 1.36 | 4.43 (4.11–4.76) | 0.40 | 1.32 (1.17–1.49) | 0.87 |
| BQ.1.1 | 2.00 (1.90–2.11) | 0.89 | 6.62 (6.31–6.95) | 0.60 | 1.30 (1.19–1.42) | 0.86 |
| BJ.1 | 3.22 (2.52–4.11) | 1.44 | 1.56 (1.35–1.80) | 0.14 | 1.18 (1.03–1.35) | 0.78 |
| XBB.1 | 2.76 (2.32–3.25) | 1.23 | 3.87 (3.08–4.85) | 0.35 | 0.94 (0.80–1.11) | 0.62 |
| BA.2.3.20 | 2.94 (2.82–3.06) | 1.31 | 4.27 (3.97–4.60) | 0.39 | 1.15 (1.11–1.19) | 0.76 |
| BA.2.75.5 | 2.15 (1.91–2.40) | 0.96 | 1.92 (1.66–2.21) | 0.17 | 0.83 (0.79–0.87) | 0.55 |
| XBB | 1.90 (1.76–2.05) | 0.85 | 2.70 (2.38–3.05) | 0.24 | 0.69 (0.63–0.76) | 0.46 |
| XAY.1 | 3.44 (3.18–3.72) | 1.54 | 4.48 (4.13–4.85) | 0.40 | 0.75 (0.71–0.79) | 0.50 |
| XBC | 0.92 (0.85–0.99) | 0.41 | 1.89 (1.74–2.33) | 0.17 | 0.73 (0.68–0.78) | 0.48 |
| BN.1.9 | 2.19 (1.84–2.58) | 0.98 | 2.36 (2.13–2.62) | 0.21 | 0.59 (0.56–0.62) | 0.39 |
| BN.1.5 | 1.67 (1.46–1.89) | 0.75 | 4.21 (3.63–4.86) | 0.38 | 0.69 (0.64–0.74) | 0.46 |
| XBB.1.5 | 2.19 (2.04–2.36) | 0.98 | 5.18 (4.61–5.80) | 0.47 | 1.20 (1.13–1.28) | 0.79 |
The in vitro half inhibitory concentration (IC50) values and 95% confidence interval (CI) were determined using high-content imaging analysis, which calculated infectivity ratio (infected cells/total cells) based on the seven concentrations of each drug treatment, and fold changes were calculated compared with the reference strain. The median IC50 and 95% CI values for remdesivir (n = 21), molnupiravir (n = 12), and nirmatrelvir (n = 13) against the reference strain were determined, and the normality test of the data was performed using the D'Agostino-Pearson normality test. All the experiments were performed in triplicate, and the quality of the high-content imaging assay was assessed by Z′ factor (Z > 0.5) using Harmony 4.9 (PerkinElmer Software).
The IC50-fold change value was represented as a relative value compared with the reference strain.
EIDD-2801 (an orally bioavailable prodrug of EIDD-1931).