7NTV

Crystal structure of SARS CoV2 main protease in complex with DN_EG_002 (modelled using PanDDA event map)

7NTV の概要

• エントリーDOI: 10.2210/pdb7ntv/pdb
• 分子名称: 3C-like proteinase, DIMETHYL SULFOXIDE, 2-acetamido-N-cyclopropyl-5-phenyl-thiophene-3-carboxamide, ... (4 entities in total)
• 機能のキーワード: protease, complex, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68498.40

構造登録者

Oerlemans, R.,Eris, D.,Wang, M.,Sharpe, M.,Domling, A.,Groves, M.R. (登録日: 2021-03-10, 公開日: 2021-06-16, 最終更新日: 2024-10-16)

主引用文献

Sutanto, F.,Shaabani, S.,Oerlemans, R.,Eris, D.,Patil, P.,Hadian, M.,Wang, M.,Sharpe, M.E.,Groves, M.R.,Domling, A.
Combining High-Throughput Synthesis and High-Throughput Protein Crystallography for Accelerated Hit Identification.
Angew.Chem.Int.Ed.Engl., 60:18231-18239, 2021

PubMed Abstract: Protein crystallography (PX) is widely used to drive advanced stages of drug optimization or to discover medicinal chemistry starting points by fragment soaking. However, recent progress in PX could allow for a more integrated role into early drug discovery. Here, we demonstrate for the first time the interplay of high throughput synthesis and high throughput PX. We describe a practical multicomponent reaction approach to acrylamides and -esters from diverse building blocks suitable for mmol scale synthesis on 96-well format and on a high-throughput nanoscale format in a highly automated fashion. High-throughput PX of our libraries efficiently yielded potent covalent inhibitors of the main protease of the COVID-19 causing agent, SARS-CoV-2. Our results demonstrate, that the marriage of in situ HT synthesis of (covalent) libraires and HT PX has the potential to accelerate hit finding and to provide meaningful strategies for medicinal chemistry projects.

PubMed: 34097796
DOI: 10.1002/anie.202105584

実験手法

X-RAY DIFFRACTION (2.065 Å)