7DK1

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

Summary for 7DK1

• Entry DOI: 10.2210/pdb7dk1/pdb
• Descriptor: 3C-like proteinase, ZINC ION, DIMETHYL SULFOXIDE, ... (7 entities in total)
• Functional Keywords: sars-cov-2, main protease, zinc, mpro-zinc complex, peptide binding protein, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 2
• Total formula weight: 68476.55

Authors

Sonkar, K.S.,Panchariya, L.,Kuila, S.,Khan, W.A.,Arockiasamy, A. (deposition date: 2020-11-22, release date: 2021-06-30, Last modification date: 2023-11-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.902 Å)