Journal: Nature Communications

Article Title: Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model

doi: 10.1038/s41467-021-22580-8

Figure Lengend Snippet: a Hamsters were intranasally infected with SARS-CoV-2. MK-4482 was administered pre-infection at 12 and 2 h before infection, or post-infection starting 12 h post-infection. Treatment was continued in both groups every 12 h for 3 consecutive days. Animals were euthanized on day 4 and lungs were harvested. T = treatment (red: pre-infection and black: post-infection treatments); I = infection; S = swab samples and N = necropsy. b Oral swab samples ( N = 6 per group) were collected on days 2 and 4 post-infection and viral shedding determined by RT-PCR ( p Value Vehicle vs Pre-treatment = >0.9999, p Value Vehicle vs Post-treatment = >0.9999, One-way ANOVA, Kruskal–Wallis test). c Oral swab samples ( N = 6 per group) were titered for infectious virus (TCID 50 ) on Vero E6 cells ( p Value Vehicle vs Pre-treatment = 0.5701, p Value Vehicle vs Post-treatment = >0.9999, One-way ANOVA, Kruskal–Wallis test). d Lung viral loads ( N = 6 per group) were determined by using RT-PCR ( p Value Vehicle vs Pre-treatment = 0.0189, p Value Vehicle vs Post-treatment = 0.1032, One-way ANOVA, Kruskal–Wallis test). e Lung samples ( N = 6 per group) were homogenized and titered for infectious virus (TCID 50 ) on Vero E6 cells. Two independent lung samples were measured from each animal ( N = 12 per group) ( p Value Vehicle vs Pre-treatment = 0.0091, p Value Vehicle vs Post-treatment = 0.0102, One-way ANOVA, Kruskal–Wallis test). b – e Blue circle, vehicle control; red square, pre-infection treatment; green triangle, post-infection treatment. Summary of Results: b , c No statistical significance in virus shedding (RT-PCR or TCID 50 ) between either of the two MK-4482 treatment groups and vehicle controls. d Significant difference in lung viral loads (RT-PCR) between pre-infection group compared to the vehicle control. Although post-infection group trended towards lower levels, no significant difference between this group and vehicle control. e Infectious titers in the lungs (TCID 50 ) were significantly different between both pre-infection and post-infection groups, compared to vehicle control group, but no significance was found between treatment groups from each other. One-way ANOVA followed by Kruskal–Wallis analysis and a pairwise Wilcox test was used to analyze differences among groups. * p < 0.05, ** p < 0.008.

Article Snippet: Groups were then treated with MK-4482 (250 mg/kg) [MedChemExpress dissolved in 10 % polyethylene glycol (PEG)−400; 2.5% Cremophor RH40 in water] at 12 h and 2 h prior to infection (pre-infection group) or 12 h following infection (post-infection group).

Techniques: Infection, Reverse Transcription Polymerase Chain Reaction, Virus, Control

Journal: Nature Communications

Article Title: Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model

doi: 10.1038/s41467-021-22580-8

Figure Lengend Snippet: Hematoxylin and eosin (H&E) staining was used on lung sections to examine lung pathology post-inoculation. Immunohistochemistry (IHC) was used to detect viral antigen in the same lung sections from each animal ( N = 6 per group). a , d , g Untreated vehicle control, ( b , e , h ) pre-infection treatment with antiviral drug MK-4482 and ( c , f , i ) post-infection treatment with MK-4482. ( a – f ) H&E stain ( g , h , i ) IHC for SARS-CoV-2 nucleocapsid antibody. a Lung 20X: multifocal, moderate broncho-interstitial pneumonia. b , c Lung 20X: minimal peribronchial interstitial pneumonia. d Lung 200X epithelial cell necrosis (arrow), edema (asterisk), interstitial pneumonia (arrowhead). e , f peribronchial and interstitial infiltrates (arrow). g Lung 20X; insert 200X: numerous immunoreactive bronchiolar epithelial cells, type I and II pneumocytes and fewer macrophages. h, i Lung 20X; insert 200X: scattered to moderate numbers of immunoreactive bronchiolar epithelial cells, type I and II pneumocytes and macrophages. Pictures were taken in RGB color space (sRGB IEC61966-2.1) with a threshold set to 128. a – c , g – i Scale bar is 200μm. d – f Scale bar is 20μm.

Article Snippet: Groups were then treated with MK-4482 (250 mg/kg) [MedChemExpress dissolved in 10 % polyethylene glycol (PEG)−400; 2.5% Cremophor RH40 in water] at 12 h and 2 h prior to infection (pre-infection group) or 12 h following infection (post-infection group).

Techniques: Staining, Immunohistochemistry, Control, Infection

Journal: Nature Communications

Article Title: Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model

doi: 10.1038/s41467-021-22580-8

Figure Lengend Snippet: a A longitudinal cross section of the right lung of each animal ( N = 6 per group) was stained for viral antigen and scanned to measure the total amount of viral antigen present in the lung section. b EIDD-1931 concentrations in the lungs. a , b Blue circle, vehicle control; red square, pre-infection treatment; green triangle, post-infection treatment. Summary of results. a The area of lung staining positive for viral antigen showed a statistically significant difference between both of the MK-4482 treatment groups, compared to vehicle controls. No difference between individual treatment groups was present. (One-way ANOVA followed by Kruskal–Wallis analysis and a pairwise Wilcox test was used to analyze differences among groups. ** p < 0.008).

Article Snippet: Groups were then treated with MK-4482 (250 mg/kg) [MedChemExpress dissolved in 10 % polyethylene glycol (PEG)−400; 2.5% Cremophor RH40 in water] at 12 h and 2 h prior to infection (pre-infection group) or 12 h following infection (post-infection group).

Techniques: Staining, Control, Infection