MPD2

MPD2 is a Cereblon-binding ligand-based PROTAC that degrades MPro, the main protease of SARS-CoV-2. MPD2 effectively reduced MPro protein levels in 293T cells in a time-dependent manner (DC50=296 nM). MPD2 exhibited potent antiviral activity against multiple SARS-CoV-2 strains and had enhanced potency against Nirmatrelvir resistant strains. MPD2 provides a new direction for antiviral drug development against SARS-CoV-2 and other emerging coronavirus pathogens (Sturcture Note: (Blue: Cereblon ligand (HY-14658), Black: linker (HY-W275882); Red: SARS-CoV-2 MPro Inhibitor MP18 (HY-158763) ).

C51H68N6O13

973.12

O=C(OCC1=CC=CC(OCCCCCCOC2=CC=CC(C(N3C(CC4)C(NC4=O)=O)=O)=C2C3=O)=C1)N[C@@H]([C@H](OC(C)(C)C)C)C(N[C@@H](CC5CCCCC5)C(N[C@@H](C[C@H]6C(NCC6)=O)C=O)=O)=O

PROTACs; SARS-CoV

Room temperature