Journal: Journal of Medicinal Chemistry

Article Title: Efficient Crystallization of Apo Sirt2 for Small-Molecule Soaking and Structural Analysis of Ligand Interactions

doi: 10.1021/acs.jmedchem.4c02896

Figure Lengend Snippet: Overall structure of Sirt2 and chemical structures of selected Sirt2 inhibitors. (A) Structural features of h Sirt2 (structure from PDB 4RMG ) shown as cross-section surface representation. Highlighted are the Rossmann-fold domain (pale cyan) with its NAD + binding site (A-, B- and C-pocket, pale yellow), the Zn 2+ -binding domain (pale green) and the acyl-lysine channel (light pink) located at the interface of the two domains. (B) A selection of published Sirt2 inhibitors. (I) Small molecule Sirt2 inhibitors SirReal2 and the improved analogue Mz242 , a 1,2,4-oxadiazole inhibitor and FLS-359 . (II) Mechanism-based inhibitors containing a thioamide warhead. , ,

Article Snippet: NAD + was purchased from Carl Roth and SirReal2 was purchased from MedChemExpress.

Techniques: Binding Assay, Selection

Journal: Journal of Medicinal Chemistry

Article Title: Efficient Crystallization of Apo Sirt2 for Small-Molecule Soaking and Structural Analysis of Ligand Interactions

doi: 10.1021/acs.jmedchem.4c02896

Figure Lengend Snippet: Crystal structures of Sirt2 apo (PDB 9FDR) and the Sirt2– SirReal2 (PDB 9FDS) complex. (A) Superimposition of Sirt2 with an open selectivity pocket (Sirt2 = salmon, PEG = brown, PDB 9FDR), obtained via MMS experiments, and Sirt2 with closed selectivity pocket (light orange, PDB 3ZGO ). The 2 F o – F c map is depicted as a blue mesh and contoured at 1.0σ. The PEG molecule can only bind when the subpocket is present, otherwise it would clash with Leu134 and Leu138 from the hinge region. (B) Sirt2– SirReal2 structure (Sirt2 = pale green, SirReal2 = green, PDB 9FDS), obtained from soaking experiments. The 2 F o – F c map is depicted as a blue mesh and contoured at 1.0σ. (C) Superimposition of Sirt2– SirReal2 (Sirt2 = pale green, SirReal2 = green), with Sirt2– SirReal2 –NAD + (Sirt2 = chocolate, SirReal2 and NAD + = light pink, PDB 4RMG ).

Article Snippet: NAD + was purchased from Carl Roth and SirReal2 was purchased from MedChemExpress.

Techniques: Chocolate

Journal: Cell Proliferation

Article Title: Direct inhibitory effect on viral entry of influenza A and SARS‐CoV‐2 viruses by azithromycin

doi: 10.1111/cpr.12953

Figure Lengend Snippet: AZ is identified as a potential inhibitor of IAV in vitro. A, The flow chart of IAV‐luc assay. B and C, The relative inhibitory rate of on IAV‐luc infection or cell viability in A549 cells treated with candidate drugs (10 μmol/L). D, The relative cell viability in A549 cells treated with AZ (0.03125‐320 μmol/L) for 72 h. E, The relative inhibitory rate of AZ (10 μmol/L), amantadine (10 μmol/L), oseltamivir (10 μmol/L) and ribavirin (10 μmol/L) on IAV‐luc infection in A549 cells. F, The relative inhibitory rate of AZ (10 μmol/L), erythromycin (10 μmol/L), roxithromycin (10 μmol/L), midecamycin (10 μmol/L), spiramycin (10 μmol/L), acetylspiramycin (10 μmol/L), clarithromycin (10 μmol/L) and dirithromycin (10 μmol/L) on IAV‐luc infection in A549 cells. G, The relative inhibitory rate of ethanol or AZ (2.5 or 5 μmol/L) on IAV‐luc infection in HEK 293T/Hela/A549 cells. H, The relative mRNA level of NP in A549 cells treated with ethanol or AZ (2, 10, 50 μmol/L) and infected with WSN (MOI = 0.001 or 0.01) for 12 h. Solvent was treated as Ctrl. I, The dose‐dependent relative inhibitory rate of AZ on WSN/H5N1/H7N9 pseudovirus infection in A549 cells. Solvent (Ethanol, DMSO or H 2 O) was treated as control (Ctrl). All results are representative of three replicate experiments. ns, no significant, * P < .05, ** P < .01, *** P < .001, **** P < .0001

Article Snippet: Oseltamivir, midecamycin, spiramycin, acetylspiramycin, clarithromycin, dirithromycin, tamoxifen, fluvastatin, fluoxetine and clemastine were obtained from MedChemExpress.

Techniques: In Vitro, Infection, Solvent, Control

Journal: Cell Proliferation

Article Title: Direct inhibitory effect on viral entry of influenza A and SARS‐CoV‐2 viruses by azithromycin

doi: 10.1111/cpr.12953

Figure Lengend Snippet: AZ has antiviral activity against SARS‐CoV‐2 pseudovirus in vitro. A, The infectivities of SARS‐CoV and SARS‐CoV‐2 pseudovirus in WT and human ACE2 stably expressed HEK293T cells. B, The relative inhibitory rate of AZ (10 μmol/L), erythromycin (10 μmol/L), roxithromycin (10 μmol/L), midecamycin (10 μmol/L), spiramycin (10 μmol/L), acetylspiramycin (10 μmol/L), clarithromycin (10 μmol/L), dirithromycin (10 μmol/L), chloroquine (CQ, 10 μmol/L) and NH 4 Cl (10 mmol/L) on SARS‐CoV‐2 pseudovirus infection in HEK293T‐ACE2 cells. C, The relative cell viability of HEK293T‐ACE2 cells treated with AZ (0.15625‐160 μmol/L) for 72 h. D‐G, The relative inhibitory rate on SARS‐CoV‐2, SARS‐CoV, VSV and Ebola pseudovirus infection in HEK293T‐ACE2 cells treated with AZ (0.625‐10 μmol/L). H, The relative inhibitory rate on SARS‐CoV‐2 pseudovirus infection in Caco2 cells treated with AZ (0.625‐10 μmol/L). I, The relative inhibitory rate on WT and mutant SARS‐CoV‐2 pseudovirus infection in HEK293T‐ACE2 cells treated with AZ (2 and 10 μmol/L). Solvent was treated as Ctrl. Experiments were repeated twice. ns, no significant, * P < .05, ** P < .01, *** P < .001, **** P < .0001

Article Snippet: Oseltamivir, midecamycin, spiramycin, acetylspiramycin, clarithromycin, dirithromycin, tamoxifen, fluvastatin, fluoxetine and clemastine were obtained from MedChemExpress.

Techniques: Activity Assay, In Vitro, Stable Transfection, Infection, Mutagenesis, Solvent