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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Chem+Commun+(Camb) 2021 ; 57 (78): 10083-10086 Nephropedia Template TP
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Zinc(2+) ion inhibits SARS-CoV-2 main protease and viral replication in vitro #MMPMID34514483
Chem Commun (Camb) 2021[Sep]; 57 (78): 10083-10086 PMID34514483show ga
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(2+) complex at 1.9 A and provide the structural basis of viral replication inhibition. We show that Zn(2+) 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(2+) complex. Further, the natural ionophore quercetin increases the anti-viral potency of Zn(2+). As the catalytic dyad is highly conserved across SARS-CoV, MERS-CoV and all variants of SARS-CoV-2, Zn(2+) mediated inhibition of Mpro may have wider implications.
Chem+Commun+(Camb) 2021 ; 57 (78): 10083-10086
