Enantioselective inhibition of the SARS-CoV-2 main protease with rhenium(i) picolinic acid complexes

Abstract

Infections of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have triggered a global pandemic with millions of deaths worldwide. Herein, the synthesis of functionalized Re(I) tricarbonyl complexes as inhibitors...

Silver N-heterocyclic carbene complexes are potent uncompetitive inhibitors of the papain-like protease with antiviral activity against SARS-CoV-2

“…8,11 Strong inhibition of this enzyme has also been reported for bismuth compounds 10 or zink pyrithione. 29 Inhibition of different SARS-CoV-2 enzymatic targets has been demonstrated for a small number of metal complexes, with helicase for bismuth 9,10 compounds, the spike/ACE2 interaction for titanocene dichloride and polyoxometalates, 8 3CL pro (M pro ) for bismuth, 10 rhenium, 30 zinc, 31 gold, 32 mercury 33 and ferrocene 34 complexes, and nsp14 N7-methyltansferase for gold and mercury complexes. 35…”

MetalDock: An Open Access Docking Tool for Easy and Reproducible Docking of Metal Complexes

“…To test the predictive power of MetalDock, we performed a case study on a recently discovered enantioselective rhenium inhibitor . The main target of this inhibitor was the 3-chymotrypsin-like protease (3CL pro ), which is considered to be one of the main targets of the SARS-CoV-2 virus.…”

“…Metal–organic compounds have been shown to be a versatile class of molecules that can be used as reagents or catalysts. , However, they also show the ability to interact with biomolecules such as proteins or DNA . The latter property can be of special interest for the development of new bioactive molecules such as anticancer (pro)­drugs. − The introduction of a metal atom into a small-molecule drug can lead to biological activity via two interaction pathways. First, the metal center may be coordinatively saturated, in which case it is often thought of as a sort of hypervalent carbon atom directing the organic functional groups of its ligands toward the protein interior.…”

Novel Re(I) Complexes as Potential Selective Theranostic Agents in Cancer Cells and In Vivo in Caenorhabditis elegans Tumoral Strains

“…Cancer stands as the second leading cause of death worldwide, contributing to a significant global disease burden with approximately 10 million annual deaths. , Conventional cancer treatments, such as surgery, radiotherapy, and chemotherapy, have notable limitations, including severe side effects on healthy organs and drug resistance . Consequently, discovering of alternative and more selective anticancer drugs is a highly desirable goal and remains to be an active field of research, where metallopharmaceuticals are playing a significant role. − Smart drugs that provide a combination of diagnostics and therapy, “theranostic agents”, are of recent origin and have also received a surge of research interest. , Radioactive 186 Re and 188 Re have been extensively used in clinical treatment of cancer, , and in the past decade, there has been an enormous interest in the exploitation of the rich photophysical properties of rhenium complexes for diverse imaging modalities and therapeutic biomedical applications. − In particular, rhenium carbonyl complexes have been shown to be novel anticancer agents, , inhibitors of the SARS-CoV-2 main protease, , and more recently therapeutic agents for schemia-reperfusion injury (IRI) . In general, the mechanisms of action of Re(I) anticancer complexes containing the fac -[Re(CO) 3 ] + core are quite distinct from that of conventional platinum agents, ,− that is dependent on covalent bond formation to DNA .…”