Casting a Wide Net to Fight Coronaviruses

To test this hypothesis, the researchers created a synthetic version of the substrate that normally binds to the protease's substrate-binding site—reasoning that if they could inhibit the substrate's access to the binding site by the mimic (known as suicide inhibitors), they should be able to block the protease's activity and maybe halt viral replication. By studying the structure of the protease–substrate/inhibitor complex, Yang et al. continually improved their synthetic inhibitor until it bound strongly to the protease. Using this initial inhibitor as a base, the authors designed a panel of inhibitors and identified compounds that rapidly blocked proteases from multiple coronaviruses and kept the coronaviruses from reproducing. The compounds caused no obvious damage in human cells in the experiments.