Allostery in homodimeric SARS-CoV-2 main protease.

Many enzymes work as homodimers with two distant catalytic sites, but the reason for this choice is often not clear. For the main protease M of SARS-CoV-2, dimerization is essential for function and plays a regulatory role during the coronaviral replication process. Here, to analyze a possible allosteric mechanism, we use X-ray crystallography, native mass spectrometry, isothermal titration calorimetry, and activity assays to study the interaction of M with three peptide substrates.