Structural basis of mercury‐ and zinc‐conjugated complexes as SARS‐CoV 3C‐like protease inhibitors

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Abstract
Five active metal‐conjugated inhibitors (PMA, TDT, EPDTC, JMF1586 and JMF1600) bound with the 3C‐like protease of severe acute respiratory syndrome (SARS)‐associated coronavirus were analyzed crystallographically. The complex structures reveal two major inhibition modes: Hg2+‐PMA is coordinated to C44, M49 and Y54 with a square planar geometry at the S3 pocket, whereas each Zn2+ of the four zinc‐inhibitors is tetrahedrally coordinated to the H41–C145 catalytic dyad. For anti‐SARS drug design, this Zn2+‐centered coordination pattern would serve as a starting platform for inhibitor optimization.