6G95

Crystal structure of Ebolavirus glycoprotein in complex with thioridazine

Summary for 6G95

• Entry DOI: 10.2210/pdb6g95/pdb
• Descriptor: Envelope glycoprotein, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: ebolavirus glycoprotein, thioridazine, protein drug complex, viral protein
• Biological source: Zaire ebolavirus (strain Mayinga-76) (ZEBOV); More
• Total number of polymer chains: 2
• Total formula weight: 57831.90

Authors

Zhao, Y.,Ren, J.,Fry, E.E.,Xiao, J.,Townsend, A.R.,Stuart, D.I. (deposition date: 2018-04-10, release date: 2018-05-23, Last modification date: 2024-11-13)

Primary citation

Zhao, Y.,Ren, J.,Fry, E.E.,Xiao, J.,Townsend, A.R.,Stuart, D.I.
Structures of Ebola Virus Glycoprotein Complexes with Tricyclic Antidepressant and Antipsychotic Drugs.
J. Med. Chem., 61:4938-4945, 2018

PubMed Abstract: A large number of Food and Drug Administration (FDA)-approved drugs have been found to inhibit the cell entry of Ebola virus (EBOV). However, since these drugs have various primary pharmacological targets, their mechanisms of action against EBOV remain largely unknown. We have previously shown that six FDA-approved drugs inhibit EBOV infection by interacting with and destabilizing the viral glycoprotein (GP). Here we show that antidepressants imipramine and clomipramine and antipsychotic drug thioridazine also directly interact with EBOV GP and determine the mode of interaction by crystallographic analysis of the complexes. The compounds bind within the same pocket as observed for other, chemically divergent complexes but with different binding modes. These details should be of value for the development of potent EBOV inhibitors.

PubMed: 29741894
DOI: 10.1021/acs.jmedchem.8b00350

Experimental method

X-RAY DIFFRACTION (2.31 Å)