Journal: Communications Medicine

Article Title: Targeted protein degraders of SARS-CoV-2 Mpro are more active than enzymatic inhibition alone with activity against nirmatrelvir resistant virus

doi: 10.1038/s43856-025-00863-1

Figure Lengend Snippet: a HiBiT detection results and ( b ) western blot verification results for singular TPD testing at 20 μM for 24 h in the HEK293T LVX Mpro-HiBiT reporter cells harbouring either wtMpro or mutated variants of Mpro (E166V, E166V + T21I and E166V + L50F). HiBiT assay results are presented as % luminescence vs DMSO controls. c , d Focus reduction assays in Calu-3 cells infected with SARS-CoV-2 Delta variant harbouring either wildtype Mpro ( c ) or Mpro containing nirmatrelvir-resistant mutations E166V + L50F ( d ) and treated with increasing doses of either nirmatrelvir, the TPD BP-198 or the NDMI BP-206 control. Data is presented as the number of foci per dose of drug as a % of the DMSO control. The IC 50 dose response for each drug was quantitated by linear regression analysis ± 95% CI. ** indicates a P = 0.0019 significant difference between BP-198 and BP-206 by multi-parametric two-way ANOVA. n.s = not significant. All experiments were completed to at least n = 2 with experiments completed to n = 3 for statistical analysis.

Article Snippet: The rabbit anti-SARS-CoV-2 3C-Like Protease (Mpro) antibody (51661), rabbit anti-VHL (E3X9K) monoclonal antibody and rabbit anti-GAPDH (14C10) monoclonal antibody were purchased from Cell Signaling.

Techniques: Western Blot, Infection, Variant Assay, Control