7DK1

Crystal structure of Zinc bound SARS-CoV-2 main protease

7DK1 の概要

• エントリーDOI: 10.2210/pdb7dk1/pdb
• 分子名称: 3C-like proteinase, ZINC ION, DIMETHYL SULFOXIDE, ... (7 entities in total)
• 機能のキーワード: sars-cov-2, main protease, zinc, mpro-zinc complex, peptide binding protein, hydrolase
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68476.55

構造登録者

Sonkar, K.S.,Panchariya, L.,Kuila, S.,Khan, W.A.,Arockiasamy, A. (登録日: 2020-11-22, 公開日: 2021-06-30, 最終更新日: 2023-11-29)

主引用文献

Panchariya, L.,Khan, W.A.,Kuila, S.,Sonkar, K.,Sahoo, S.,Ghoshal, A.,Kumar, A.,Verma, D.K.,Hasan, A.,Khan, M.A.,Jain, N.,Mohapatra, A.K.,Das, S.,Thakur, J.K.,Maiti, S.,Nanda, R.K.,Halder, R.,Sunil, S.,Arockiasamy, A.
Zinc 2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro.
Chem.Commun.(Camb.), 57:10083-10086, 2021

PubMed Abstract: Zinc deficiency is linked to poor prognosis in COVID-19 patients while clinical trials with zinc demonstrate better clinical outcomes. The molecular targets and mechanistic details of the anti-coronaviral activity of zinc remain obscure. We show that zinc not only inhibits the SARS-CoV-2 main protease (Mpro) with nanomolar affinity, but also viral replication. We present the first crystal structure of the Mpro-Zn complex at 1.9 Å and provide the structural basis of viral replication inhibition. We show that Zn coordinates with the catalytic dyad at the enzyme active site along with two previously unknown water molecules in a tetrahedral geometry to form a stable inhibited Mpro-Zn complex. Further, the natural ionophore quercetin increases the anti-viral potency of Zn. As the catalytic dyad is highly conserved across SARS-CoV, MERS-CoV and all variants of SARS-CoV-2, Zn mediated inhibition of Mpro may have wider implications.

PubMed: 34514483
DOI: 10.1039/d1cc03563k

実験手法

X-RAY DIFFRACTION (1.902 Å)