Gold Metallodrugs to Target Coronavirus Proteins: Inhibitory Effects on the Spike‐ACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics. Issue 66 (19th October 2020)

• Record Type: Journal Article
• Authors: Gil‐Moles, Maria; Basu, Uttara; Büssing, Rolf; Hoffmeister, Henrik; Türck, Sebastian; Varchmin, Agnieszka; Ott, Ingo
• Is Part Of: Chemistry. Volume 26:Issue 66(2020)
• Page Start: 15140
• Page End: 15144
• Publication Date: 2020-10-19
• Subjects: Auranofin -- coronavirus -- gold complexes -- metallodrugs -- SARS-CoV-2; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202004112
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: 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. Abstract : Going for gold ! Gold complexes show inhibitory effects on selected SARS‐CoV‐2 protein targets. The strong inhibition of PLpro correlates with the ability of the complexes to remove zinc from the enzyme.