6HS4

Crystal structure of Ebolavirus glycoprotein in complex with inhibitor 118

6HS4 の概要

• エントリーDOI: 10.2210/pdb6hs4/pdb
• 分子名称: Envelope glycoprotein,GP1,Envelope glycoprotein, Envelope glycoprotein, alpha-D-mannopyranose-(1-3)-[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, ... (8 entities in total)
• 機能のキーワード: ebola glycoprotein, structure-based in silico screening, compound 118, compound 118a, natural compound, viral protein
• 由来する生物種: Zaire ebolavirus (strain Mayinga-76) (ZEBOV); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58494.38

構造登録者

Ren, J.,Zhao, Y.,Stuart, D.I. (登録日: 2018-09-28, 公開日: 2019-02-27, 最終更新日: 2024-11-20)

主引用文献

Shaikh, F.,Zhao, Y.,Alvarez, L.,Iliopoulou, M.,Lohans, C.,Schofield, C.J.,Padilla-Parra, S.,Siu, S.W.I.,Fry, E.E.,Ren, J.,Stuart, D.I.
Structure-Based in Silico Screening Identifies a Potent Ebolavirus Inhibitor from a Traditional Chinese Medicine Library.
J.Med.Chem., 62:2928-2937, 2019

PubMed Abstract: Potent Ebolavirus (EBOV) inhibitors will help to curtail outbreaks such as that which occurred in 2014-16 in West Africa. EBOV has on its surface a single glycoprotein (GP) critical for viral entry and membrane fusion. Recent high-resolution complexes of EBOV GP with a variety of approved drugs revealed that binding to a common cavity prevented fusion of the virus and endosomal membranes, inhibiting virus infection. We performed docking experiments, screening a database of natural compounds to identify those likely to bind at this site. Using both inhibition assays of HIV-1-derived pseudovirus cell entry and structural analyses of the complexes of the compounds with GP, we show here that two of these compounds attach in the common binding cavity, out of eight tested. In both cases, two molecules bind in the cavity. The two compounds are chemically similar, but the tighter binder has an additional chlorine atom that forms good halogen bonds to the protein and achieves an IC of 50 nM, making it the most potent GP-binding EBOV inhibitor yet identified, validating our screening approach for the discovery of novel antiviral compounds.

PubMed: 30785281
DOI: 10.1021/acs.jmedchem.8b01328

実験手法

X-RAY DIFFRACTION (2.05 Å)