The synthetic drug ebselen can bind to both the catalytic region and a previously unknown distant site on the SARS-CoV-2 virus' main protease, according to a molecular simulation analysis of the drug's interactions with this enzyme. The results suggest that ebselen could be a potential treatment for COVID-19, if future work can confirm its ability to inhibit the activity of the viral protease, which is involved in viral gene expression and replication. While current virtual screening campaigns primarily focus on drugs that target the catalytic site of the SARS-CoV-2 main protease, the findings highlight another binding site that may provide an effective target for other drugs previously written off as ineffective. Since researchers typically require years to design and develop drugs for widespread use, repurposing previously approved pharmaceuticals is considered an essential strategy to quickly combat the current global pandemic. Recently, computational-experimental screenings identified several existing drugs, including ebselen, that may work to inhibit the virus' main protease. However, the molecular mechanisms by which this drug interacts with the main protease had yet to be understood. To investigate this interaction, Cintia Menendez and colleagues performed molecular simulations, identifying sites at which the drug and the main protease interact while evaluating the effect of different binding sites on molecular stiffness and strain. They found that ebselen appears to target both a binding site within the catalytic region and another between binding site domains II and III. Menendez et al. suggest that future experiments will be necessary to validate these findings, especially concerning the distant binding site.