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Gold Metallodrugs to Target Coronavirus Proteins: Inhibitory Effects on the Spike‐ACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics **
Author(s) -
GilMoles Maria,
Basu Uttara,
Büssing Rolf,
Hoffmeister Henrik,
Türck Sebastian,
Varchmin Agnieszka,
Ott Ingo
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202004112
Subject(s) - auranofin , protease , chemistry , enzyme , proteases , coronavirus , gold compounds , middle east respiratory syndrome coronavirus , papain , covid-19 , biochemistry , pharmacology , combinatorial chemistry , biology , medicine , immunology , rheumatoid arthritis , disease , pathology , infectious disease (medical specialty)
Gold complexes have a long tradition in medicine and for many examples antirheumatic, anticancer or anti‐infective effects have been confirmed. Herein, we evaluated the lead compound Auranofin and five selected gold organometallics as inhibitors of two relevant drug targets of severe acute respiratory syndrome coronaviruses (SARS‐CoV). The gold metallodrugs were effective inhibitors of the interaction of the SARS‐CoV‐2 spike protein with the angiotensin converting enzyme 2 (ACE2) host receptor and might thus interfere with the viral entry process. The gold metallodrugs were also efficient inhibitors of the papain‐like protease (PLpro) of SARS‐CoV‐1 and SARS‐CoV‐2, which is a key enzyme in the viral replication. Regarding PLpro from SARS‐CoV‐2, the here reported inhibitors are among the very first experimentally confirmed examples with activity against this target enzyme. Importantly, the activity of the complexes against both PLpro enzymes correlated with the ability of the inhibitors to remove zinc ions from the labile zinc center of the enzyme. Taken together, the results of this pilot study suggest further evaluation of gold complexes as SARS‐CoV antiviral drugs.