AVI8122

AVI8122 (0-100 μM; 10 min at 37 °C) potently inhibits the M^pro enzymatic activity of various coronaviruses, including SARS-CoV-2 (IC₅₀ = 0.0047 μM), MERS-CoV, HKU8, PEDV, IBV, HKU15, and human common cold coronaviruses, with its potency consistently ranging from sub-20 nM to low micromolar levels^[1].
AVI8122 (0-0.4 μM) is a tight-binding inhibitor of M^pro from SARS-CoV-2, PEDV, HKU8, IBV and HKU15, with a K_i of 0.14 nM; all K_i values fall within the low nanomolar range^[1].
AVI8122 (20 μM; 10 min at room temperature; dialyzed for up to 80 h) forms a practically irreversible complex with SARS-CoV-2 M^pro, whereas its binding to IBV M^pro and HKU8 M^pro is partially reversible, with species-dependent residence times^[1].
AVI8122 potently inhibits the replication of wild-type SARS-CoV-2 in A549-ACE2-TMPRSS2 cells (EC₅₀ = 36.9 nM), while also suppressing the replication of its variants of concern; when P-glycoprotein efflux is inhibited, the potency of this drug against the Omicron variant in Vero E6 cells is further enhanced^[1].
AVI8122 (0.02-400 μM; 24 h) inhibits the M^pro activity of SARS-CoV-2, MERS-CoV, PEDV, HKU8, IBV and HKU15 in HEK 293 cells, with an EC₅₀ of 3.1 μM against SARS-CoV-2, and its cytotoxicity is low relative to its antiviral potency^[1].
AVI8122 (0.1 nM-2 mM; 10 min at 37 °C) exhibits weak inhibitory activity against human cathepsin S, cathepsin B, and cathepsin L, with high selectivity over SARS-CoV-2 M^pro (selectivity index of 280-700)^[1].
AVI8122 exhibits favorable in vitro pharmacokinetic properties, including high metabolic stability in human liver microsomes and hepatocytes, moderate plasma protein binding in humans, high solubility, and a moderate LogD value^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.