Just Published in Chemistry - A European Journal
04.01.2022Metallodrug Profiling against SARS-CoV-2 Target Proteins Identifies Highly Potent Inhibitors of the S/ACE2 interaction and the Papain-like Protease PLpro
AUTHORS: Dr. Maria Gil-Moles, Sebastian Türck, Dr. Uttara Basu, Dr. Andrea Pettenuzzo, Dr. Saurav Bhattacharya, Ananthu Rajan, Xiang Ma, Rolf Büssing, Jessica Wölker, Dr. Hilke Burmeister, Henrik Hoffmeister, Pia Schneeberg, Andre Prause, Petra Lippmann, Josephine Kusi-Nimarko, Dr. Storm Hassell-Hart, Dr. Andrew McGown, Dr. Daniel Guest, Dr. Yan Lin, Dr. Anna Notaro, Dr. Robin Vinck, Dr. Johannes Karges, Dr. Kevin Cariou, Dr. Kun Peng, Dr. Xue Qin, Dr. Xing Wang, Dr. Joanna Skiba, Dr. Łukasz Szczupak, Prof. Dr. Konrad Kowalski, Prof. Dr. Ulrich Schatzschneider, Dr. Catherine Hemmert, Prof. Dr. Heinz Gornitzka, Prof. Dr. Elena R. Milaeva, Dr. Alexey A. Nazarov, Prof. Dr. Gilles Gasser, Prof. Dr. John Spencer, Dr. Luca Ronconi, Prof. Dr. Ulrich Kortz, Prof. Dr. Jindrich Cinatl, Prof. Dr. Denisa Bojkova, Prof. Dr. Ingo Ott
ABSTRACT: Despite their increasing relevance in medicinal chemistry, metal complexes are still underrepresented in compound screening libraries for drug discovery. In this work more than 100 metal complexes were evaluated as inhibitors of two targets in the SARS-CoV-2 life cycle, the interaction of the spike protein with the ACE2 receptor and the protease PLpro. The most active inhibitors were studied for antiviral effects in SARS-CoV-2 infected cells and led to the discovery of active compounds that will provide starting points for future drug design.
LINK: https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202103258
