XR8-23

XR8-23 is a small molecule inhibitor targeting the papain-like protease (PLpro) of SARS-CoV-2, an essential enzyme for viral replication and immune evasion. Developed initially by the University of Arizona, with research contributions from Sunshine Biopharma, XR8-23 demonstrates submicromolar potency (IC50 = 0.39 µM) against PLpro and exhibits broad-spectrum antiviral activity against multiple variants of concern including WA1/2020, Gamma (P.1), Delta (B.1.617.2), and Omicron (BA.1). The compound shows over tenfold selective accumulation in lung tissue compared to plasma in mouse models and has demonstrated in vivo efficacy at a dose of 10 mg/kg via repeated intravenous injections[3][4][5]. Structurally, it features a basic amine side chain extending from a thiophene group that contributes to its strong binding affinity and slow dissociation rate from PLpro[5]. Its mechanism involves noncovalent inhibition at the BL2-groove adjacent to the active site of PLpro, enforcing closure of the active site pocket[4][5]. As of mid-2025, XR8-23 remains in preclinical development for coronavirus infections.

Other names

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