Journal: Scientific Reports

Article Title: Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease

doi: 10.1038/s41598-021-02432-7

Figure Lengend Snippet: Capmatinib has a broad range of antiviral activity against human coronaviruses. ( A ) Quantification of 229E Spike protein abundance in MRC-5 cells treated with increasing doses of capmatinib in the IF assay (48 h infection), as mean ± SE (n = 3) expressed relative to DMSO (vehicle) control. * P < 0.05 relative to control ( B ) (left) Representative images of 229E plaques observed in MRC-5 cells treated with 10 µM capmatinib or DMSO (vehicle) for 6 days. (right) Quantification of viral titer from the DMSO (vehicle) control or capmatinib plaque assays, expressed as PFU/mL. * P < 0.05 relative to control ( C ). (left) Representative images of NL63 plaques observed in LLC-MK2 treated with 10 µM capmatinib or DMSO (vehicle) control for 5 days. (right) Quantification of NL63 PFU/mL in LLC-MK2 cells treated with the indicated doses of capmatinib. * P < 0.05 relative to control ( D ). Relative NL63 N protein RNA abundance 3 days post-infection in LLC-MK2 cells treated with 10 µM capmatinib relative to DMSO (vehicle) control. * P < 0.05 relative to control, n = 3 experimental replicates. E (left) Representative images of OC43 plaques observed in LLC-MK2 cells treated with 10 µM capmatinib or DMSO (vehicle) for 5 days. (right) Quantification of OC43 PFU/mL in LLC-MK2 cells treated with capmatinib or DMSO (vehicle) control. * P < 0.05 relative to control.

Article Snippet: CoronaGrow LLC-MK2 (kidney epithelial) cells, a subclonal line of parental LLC-MK2 cells were obtained from VectorBuilder Inc. (Chicago, IL, Cat. No. CL0004).

Techniques: Activity Assay, Infection

Journal: Scientific Reports

Article Title: Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease

doi: 10.1038/s41598-021-02432-7

Figure Lengend Snippet: 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.

Article Snippet: CoronaGrow LLC-MK2 (kidney epithelial) cells, a subclonal line of parental LLC-MK2 cells were obtained from VectorBuilder Inc. (Chicago, IL, Cat. No. CL0004).

Techniques: Activity Assay, Infection, Expressing, Neutralization, Transfection