Zinc2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro
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 protea...
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| Veröffentlicht in: | Chemical communications (Cambridge, England) England), 2021-10, Vol.57 (78), p.10083-10086 |
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| creator | Love Panchariya Wajahat Ali Khan Kuila, Shobhan Sonkar, Kirtishila Sahoo, Sibasis Ghoshal, Archita Kumar, Ankit Verma, Dileep Kumar Hasan, Abdul Mohd Azeem Khan Jain, Niyati Mohapatra, Amit Kumar Das, Shubhashis Thakur, Jitendra K Maiti, Souvik Nanda, Ranjan Kumar Halder, Rajkumar Sujatha Sunil Arockiasamy, Arulandu |
| description | 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 Å 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. |
| doi_str_mv | 10.1039/d1cc03563k |
| format | Article |
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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 Å 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+. 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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 Å 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+. 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| source | Royal Society Of Chemistry Journals 2008-; Alma/SFX Local Collection |
| subjects | Crystal structure Protease Replication Severe acute respiratory syndrome coronavirus 2 Water chemistry Zinc |
| title | Zinc2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro |
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