Fig 4.

Therapeutic pyronaridine protects against lethal infection by mouse-adapted SARS-CoV-2 in old mice. Six-month-old wild-type BALB/c mice were treated with pyronaridine(oral administration), or a phosphate-buffered saline vehicle control daily at the indicated concentrations starting 1 h post-infection. Mice (n = 5 per group) were intranasally inoculated with 1 × 10⁴ PFU per mouse of mouse-adapted SARS-CoV-2 (MA-10). (A–F) Mice were weighed daily (A), clinical scores for disease severity were recorded daily (B), lethality or survival was recorded daily (C), lungs were analyzed for viral titer 2 days after infection by plaque assay (D), or fixed in 4% paraformaldehyde for H&E staining and quantified for interstitial and bronchovascular inflammation (E and F). Mean ± SD is shown. *P < 0.05, **P < 0.01, and ***P < 0.001, with blue asterisks indicating differences with the vehicle control group. Lung titers were analyzed for significance by log transformation and paired t-test analysis. A comparison of survival curves was done with log-rank (Mantel-Cox) test.