SARS-CoV-2 is a novel coronavirus that has led to millions of infected people worldwide. The SARS-CoV-2 pandemic has created a need for new antivirals in combating the virus, especially for those not vaccinated. The potential antivirals being worked on in our group consist of a cobalt (III) or copper (II) centers bound to an aromatic Schiff-base. The compounds we developed are proposed to inhibit the activity of the Papain-Like Protease (PLPro) by interacting with the PLPro zinc finger domain. This binding then deactivates PLPro and prevents further virus replication. The proposed mechanism for inhibition is dependent on the complex family under consideration. For the cobalt (III) complex family, this involves the exchange of a liable aqua ligand for a cysteine protein residue previously bound to the zinc ion in the (cys)4Zn active site. For the copper(II) complex family, the oxygen atoms coordinate to and thus extract the zinc ion from the (cys)4Zn active site. Inhibition of PLPro by as much as 48% in an in vitro assay has been demonstrated by these complexes administered at a concentration of 10 µM.

Inhibiting SARS-CoV-2 zinc finger protein using CoIII and CuII schiff-base complexes

ACS Spring 2022

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