Dimethyl sulfoxide (DMSO) affects activity of SARS-CoV-2 main protease

The SARS-CoV-2 main protease (re) is necessary for viral replication and is therefore the subject of intense inhibitor development efforts. We find that this enzyme is active at very high concentrations of dimethyl sulfoxide (DMSO), a common co-solvent for inhibitor candidates. The enzyme has enhanced activity with increasing DMSO, reaching a maximum at 33%. The impact of this additive has a profound effect on activity assays: in water/DMSO solutions, modest inhibitors appear to be inactive, while poor inhibitors appear to act as agonists.