Figure 4
The antiviral activity of capmatinib is not attributed to its canonical role as an inhibitor of MET. (A) (left) Representative images of plaques in LLC-MK2 cells treated with 10 µM capmatinib, 10 µM AMG-337, or DMSO (vehicle) control and infected with NL63 for 5 days and (right) quantification of NL63 viral titer, shown as mean PFU ± SE (n = 3 with 3 technical replicates per experiment). (B) (left) Representative images of plaques in LLC-MK2 cells treated with DMSO (vehicle) control, 10 µM capmatinib, or 10 µM AMG-337, and infected with OC43 and (right) quantification of OC43 viral titer shown as mean PFU ± SE (n = 3 with 3 technical replicates per experiment). (C) (left) Representative images from IF assay of MRC-5 cells treated with 10 µM capmatinib or AMG-337 and infected with 229E. (right) Quantification of 229E S protein expression (20 images per condition, n = 3). (D) Representative neutralization curves from n = 5 independent experiments showing the relative antiviral activity of capmatinib vs. AMG-337 in pseudovirus assays performed with the SARS-CoV-1 and SARS-CoV-2 Spike protein. (E) Structures of capmatinib and AMG-337. (F) (left) Representative images of plaques in LLC-MK2 cells treated with 10 µM JH-I-25 and infected with OC43 for 5 days and (right) quantification of the OC43 viral titer shown as mean PFU ± SE (n = 3 with 3 technical replicates per experiment). (G) (left) Representative images from MRC-5 cells treated with 10 µM JH-I-25 and infected with 229E for 2 days and (right) quantification of 229E Spike protein expression (10 images per condition, n = 3). H (left) Representative images of MRC-5 cells transfected with IRAK1/4 siRNA or control and infected with 229E for 2 days. (right) Quantification of 229E Spike protein expression shown as mean ± SE, expressed relative to DMSO (vehicle) control (n = 3). *P < 0.05.
