UC San Diego

Since its outbreak, the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has impacted the quality of life and cost hundreds-of-thousands of lives worldwide. Based on its global spread and mortality, there is an urgent need for novel treatments which can combat this disease. To date, the 3-chymotrypsin-like protease (3CL^pro ), which is also known as the main protease, is considered among the most important pharmacological targets. The vast majority of investigated 3CL^pro inhibitors are organic, non-covalent binders. Herein, the use of inorganic, coordinate covalent binders is proposed that can attenuate the activity of the protease. Re^I tricarbonyl complexes were identified that demonstrate coordinate covalent enzymatic inhibition of 3CL^pro . Preliminary studies indicate the selective inhibition of 3CL^pro over several human proteases. This study presents the first example of metal complexes as inhibitors for the 3CL^pro cysteine protease.