Tafenoquine [TQ] exhibited EC50/90s of approximately 2.6/5.1 microM against SARS-CoV-2 in VERO E6 cells and was 4-fold more potent than hydroxychloroquine [HCQ]. Time-of-addition experiments were consistent with a different mechanism for TQ v HCQ. Physiologically based pharmacokinetic (PBPK) modeling suggested that lung unbound concentrations of TQ in COVID-19 patients may exceed the EC90 for at least 8 weeks after administration. The therapeutic potential for TQ in management of COVID-19 should be further evaluated.Competing Interest StatementGSD is the majority equity holder in 60 Degrees Pharmaceuticals LLC [60P] which has a financial interest in the commercial success of tafenoquine. GSD is an inventor on several tafenoquine-related COVID 19 patents, for which ownership interest has been assigned to 60P. AL and JF are employees of 360 Biolabs and have no personal financial relationship to 60P. CR, KRY, and DW are employees of Certara and have no personal financial relation with 60P or the Gates Foundation. 60P provided funding for antiviral assays performed by 360 Biolabs under contract. The Gates Foundation [BGMF] provided funding for the pharmacokinetic modeling.
Collection : COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv