Leritrelvir (RAY1216) is an orally active SARS-CoV-2 main protease slow-tight inhibitor with a Ki of 8.6 nM.
Cmax: the maximum observed concentration of the drug collected in bodily material from subjects in a clinical study
Tmax: the time it takes to reach the maximum concentration or time to Cmax
AUC: “Area Under the Curve” and represents the total exposure of the drug experienced by the subject in a clinical study
Cl: total plasma clearance
Vdss: Steady state volume of distribution
T1/2: Half-time is the time it takes for half the drug concentration to be eliminated
oral (F%): Oral bioavailability
Leritrelvir (RAY1216) has a drug-target residence time of 104 min[1].
Leritrelvir is covalently attached to the catalytic Cys145 through the α-ketoamide warhead[1].
Leritrelvir (0-1000 nM; 72 h) shows antiviral activities against SARS-CoV-2 wild type ancestral strain and variants[1].
Leritrelvir (RAY1216 (150-600 mg/kg/day; i.g.; 5 days) effectively prolongs survival of SARS-CoV-2 infected mice[1].
Compound pharmacokinetics parameters in different animal species[1]
| Compound | Species | dose (mg/kg) | Cmax (nM) | Tmax (h) | AUC(0-last) (nM•h) | Cl (mL/min/kg) | Vdss (L/kg) | T1/2 (h) | oral F (%) |
| Mouse | 3.0 (IV) | - | - | 7789 | 10 | 1.4 | 3.8 | - | |
| 10 (PO) | 1287 | 2.0 | 5698 | - | - | 2.6 | 22 | ||
| RAY1216 | rat | 2.0 (IV) | - | - | 4505 | 12.5 | 1.1 | 2.2 | - |
| 10 (PO) | 916 | 0.9 | 7429 | - | - | 4.3 | 33 | ||
| cynomolgus macaque | 1.0 (IV) | - | - | 1157 | 22.5 | 1.0 | 0.9 | - | |
| 5.0 (PO) | 102 | 1.5 | 458 | - | - | 14.9 | 8 |
Cmax: the maximum observed concentration of the drug collected in bodily material from subjects in a clinical study
Tmax: the time it takes to reach the maximum concentration or time to Cmax
AUC: “Area Under the Curve” and represents the total exposure of the drug experienced by the subject in a clinical study
Cl: total plasma clearance
Vdss: Steady state volume of distribution
T1/2: Half-time is the time it takes for half the drug concentration to be eliminated
oral (F%): Oral bioavailability
References:
[1]. Chen X, et al. Inhibition mechanism and antiviral activity of an α-ketoamide based SARS-CoV-2 main protease inhibitor. bioRxiv, 2023: 2023.03. 09.531862.