Zinc2+ion inhibits SARS-CoV-2 main protease and viral replicationin vitro
| Autor: | Love Panchariya, Kirtishila Sonkar, Jitendra K. Thakur, Wajahat Ali Khan, Archita Ghoshal, Dileep Kumar Verma, Ankit Kumar, A. Arockiasamy, Mohd Azeem Khan, Rajkumar Halder, Sibasis Sahoo, Souvik Maiti, Abdul Hasan, Sujatha Sunil, Niyati Jain, Amit Kumar Mohapatra, Shubhashis Das, Ranjan Kumar Nanda, Shobhan Kuila |
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| Rok vydání: | 2021 |
| Předmět: |
Protease
biology viruses medicine.medical_treatment Metals and Alloys Ionophore Active site chemistry.chemical_element General Chemistry Zinc medicine.disease Catalysis In vitro Surfaces Coatings and Films Electronic Optical and Magnetic Materials Cell biology Viral replication chemistry Materials Chemistry Ceramics and Composites medicine biology.protein Zinc deficiency Binding site |
| Zdroj: | Chemical Communications. 57:10083-10086 |
| ISSN: | 1364-548X 1359-7345 |
| DOI: | 10.1039/d1cc03563k |
| Popis: | 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-Zn2+ complex at 1.9 A and provide the structural basis of viral replication inhibition. We show that Zn2+ 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-Zn2+ complex. Further, the natural ionophore quercetin increases the anti-viral potency of Zn2+. As the catalytic dyad is highly conserved across SARS-CoV, MERS-CoV and all variants of SARS-CoV-2, Zn2+ mediated inhibition of Mpro may have wider implications. |
| Databáze: | OpenAIRE |
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