Related Articles Crystal structure of SARS CoV 2 main protease provides a basis for design of improved ketoamide inhibitors Science 2020 Mar 20 Authors Zhang L Lin D Sun X Curth U Drosten C Sauerhering L Becker S Rox K Hilgenfeld R Abstract The COVID 19 pandemic caused by SARS CoV 2 is a global health emergency An attractive drug target among coronaviruses is the main protease Mpro 3CLpro due to its essential role in processing the polyproteins that are translated from the viral RNA We report the X ray structures of the unliganded SARS CoV 2 Mpro and its complex with an ketoamide inhibitor This was derived from a previously designed inhibitor but with the P3 P2 amide bond incorporated into a pyridone ring to enhance the half life of the compound in plasma Based on the structure we developed the lead compound into a potent inhibitor of the SARS CoV 2 Mpro The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route PMID 32198291 PubMed as supplied by publisher