Potent inhibition of SARS-CoV-2 proteases PLpro and 3CLpro by selected gold(III)-dithiocarbamato complexes showing strong and selective antiviral activity against HCoV-OC43.

Selected gold(III)-dithiocarbamato complexes were identified as potent inhibitors of two critical enzymes involved in the SARS-CoV-2 replication cycle, the papain-line protease (PLpro) and the 3-chymotrypsin-like protease (3CLpro), showing exceptional inhibition of PLpro with IC50 values in the range of 0.1-0.2 μM and rather moderate activity against 3CLpro (IC50 values 8-9 μM). Crucially, the inhibitory activity could be attributed to the presence of the gold(III) centre, as the gold-free dithiocarbamato ligand showed no significant activity against either proteases. The toxicity toward host cells, cellular uptake, and antiviral activity against the HCoV-OC43 coronavirus of the complexes were generally in good correlation to one another. Complexes Au-1 and Au-2 stood out as a highly active antiviral agents with a selectivity index above 90.