Caspase 3/7 activity for the phenotypic resistance testing of SARS-CoV-2 strains
(A) Drug dose-response curves and concentrations that reduce cellular levels of the SARS-CoV-2 S protein by 50% (IC50) in Caco-2-F03 and Calu-3 cells as determined by immunostaining 24 h (Caco-2-F03) or 48 h (Calu-3) postinfection with the SARS-CoV-2 strain FFM3 or its remdesivir-adapted substrain FFM3rREM at MOI 0.01.
(B) Drug concentrations that reduce caspase 3/7 activity in FFM3 and FFM3rREM (MOI 0.01)-infected Caco-2-F03 cells 48 h postinfection. P-values were determined by Student’s t-test.
(C) Sequence variants in FFM3rREM compared to FFM3.
(D) The polymerase complex with nsp7 and nsp8 and a template-primer RNA (cyan and deep teal) and remdesivir (magenta) bound. Gly671Ser is shown in red (as serine).
(E) The SARS-CoV-2 polymerase Gly671Ser sequence variant. Residue 671 is shown in red as serine, which would be able to form a hydrogen bond with Thr402 which would not be present as Gly671. All p values were calculated by two-way ANOVA.
Results are expressed as the mean ± standard deviation.