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. 2022 Mar 22:eabm3410. doi: 10.1126/scitranslmed.abm3410

Fig. 1. The chemical structure and in vitro potency of GS-621763 in comparison to RDV (GS-5734) and GS-441524.

Fig. 1.

(A to C) The chemical structures of the parent adenosine nucleoside analog GS-441524 (A), the monophosphoramidate prodrug RDV (B), and GS-621763, the tri-isobutyryl ester of GS-441524 (C) are shown. (D) The mean percent inhibition of SARS-CoV-2 replication by GS-621763, in comparison to the prodrug RDV and the parental nucleoside GS-441524 in A459-hACE2 cells is shown (triplicate samples were analyzed). (E) Cytotoxicity was measured in A459-hACE2 cells treated with GS-621763, RDV, and GS-441524 (triplicate samples were analyzed). (F) Inhibition of SARS-CoV-2-fLUC replication by GS-621763, RDV, and the parental nucleoside GS-441524 in normal human bronchial epithelial (NHBE) cultures is shown (duplicate samples were analyzed). (G) In vitro EC50 values are shown for inhibition of viral replication by GS-621763, RDV, and the parental nucleoside GS-441524 in A459-hACE2 and NHBE cells. Data are presented as mean ± SD. For (D to F), the horizontal dashed line indicates 50% inhibition on the X-axis and the dotted line indicates 0% inhibition on the X-axis.