Fig. 1.

Evaluation of the therapeutic efficacy of nirmatrelvir, remdesivir and molnupiravir monotherapies and their combinations, nirmatrelvir-remdesivir and nirmatrelvir-molnupiravir in SARS-CoV-2 infected K18-hACE2 transgenic mice. (A) Schematic illustration of the study design. Mice were infected with 5 MLD50 of SARS-CoV-2 followed by administration of 20 mg/kg drugs for 5 consecutive days. Disease progression and other clinical parameters were monitored until 14 DPI, and the brain and lung were collected at 5 DPI for viral titer estimation and histopathological and immunohistochemical analyses. (B) Body weight was monitored daily for 14 days and is expressed as a percentage relative to the initial body weight on day 0. (C) Kaplan–Meier plot of the survival of all the groups (log-rank Mantel-Cox; **p < 0.01, ***p < 0.001). (D) The clinical score was evaluated by assessing appearance (fur, eye closure), activity and movement from 0 DPI to 14 DPI, and the cumulative clinical score of mice in each group is indicated.