The twenty molecules with the best helicase binding affinity are summarized in Table . The compounds can be broadly characterized as containing one or more hydrophobic aromatic moieties linked to another polycyclic moiety containing hydrogen bond donors or acceptors. The top-ranked molecules come from diverse drug classes, with antiviral agents making up 25% of the hits and antihistamines and antipsychotics also being well represented. The remaining high binding hits included drugs and natural products used to treat a diverse range of afflictions including cancers, infections, coagulation disorders, and hypertension. Several of the top hits from our screen had experimental their SARS-CoV-2 activity determined, as do ~30% of the 87 shortlisted compounds from our docking studies (Supplementary Table )