Sunday, August 08, 2021 11:01:24 PM
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8260826/
Mirza et al.115 reported compound Z93 as a potential human ubiquitin-specific protease 2 (USP2) inhibitor through integrated in silico efforts. USP2 inhibitors, such as thiopurine analogs, have been reported to inhibit SARS-CoV PLpro. However, based on the above results, it can only be speculated that Z93 might be a potential chemical lead targeting SARS-CoV-2 PLpro, thus warranting further evaluation in vitro. Additionally, the Pegan group109 declared that naphthalene-based inhibitors [48 (6 in Ref. 109) and GRL-0617, Fig. 5A-
A-2
2 (48, 49)] showed inhibitory activity against SARS-CoV-2 PLpro and antiviral anctivity with IC50s of 21.0 and 27.6 µmol/L, respectively (Table 2). Gao et al.116 showed that GRL-0617 was effective in inhibiting SARS-CoV-2 PLpro activity with an IC50 of 2.2 ± 0.3 µmol/L and that its mechanism of action was not limited to occupying the substrate pockets, but rather extended to sealing the entrance to the substrate binding cleft, thereby preventing the binding of the substrate. Another team reported that GRL-0617 showed a promising inhibitory activity against SARS-CoV-2 PLpro in vitro with an IC50 of 2.1 µmol/L and effective antiviral inhibition of SARS-CoV-2 in cell-based assays. No apparent cytotoxicity of GRL-0617 on Vero E6 cells was observed with concentrations up to 100 µmol/L117.
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