Figure 6.
Investigation of the anti-SARS-CoV-2 effects of the PHGDH inhibitor NCT-503 alone or in in combination with 2-Deoxy-D-glucose (2DG)
(A–E) Scheme of the testing of NCT-503 for anti-SARS-CoV-2 activity in air liquid interface (ALI) cultures of primary human bronchial epithelial (HBE) cells. Effect of NCT-503 on (B) caspase 3/7 activity, (C) virus titers (determined as genomic RNA copy numbers by qPCR), (D) transepithelial electrical resistance (TEER), and (E) LDH release in ALI HBE cultures infected with Delta (MOI 1) 120 h postinfection.
(F) Anti-SARS-CoV-2 effects of NCT-503 in combination with 2-Deoxy-D-glucose (2DG). Illustration of how NCT-503 and 2DG can exert combined effects on a common metabolic pathway.
(G) Representative fluorescence images indicating the number of Delta- and Omicron (MOI 0.01)-infected cells in NCT503 and/or 2DG-treated Caco-2-F03 cultures 24 h postinfection.
(H) and I) Weighted combination indices (CIwt) determined by the method of Chou and Talalay66 indicating a strong synergism of NCT-503 and 2DG.
Results are expressed as the mean ± standard deviation.