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. 2022 Apr 6;13(12):940–953. doi: 10.1007/s13238-022-00909-3

Figure 4.

Figure 4

Antiviral efficacy of F0213 in animal models. (A–E) F0213 improves lung pathogenesis in a SARS-CoV-2 hamster model. (A) Therapeutic treatment used oral (PO) or intraperitoneal (IP) administration of F0213 (5 mg/kg), given at 6 hpi, 24 hpi and 48 hpi after virus challenge at day 0. Lung tissue samples were collected at 4dpi. GS-441524 (40 mg/kg) was included as a control via IP route. Vehicle contains 2% DMSO in 12% SBE-β-CD and by IP injection. (B and C) Viral yields in hamster lungs were determined by plaque assay (B) and RT-qPCR assay (C), respectively. (D) Representative images of infected cells by immunofluorescence staining in lung. SARS-CoV-2 N expression (green) is shown in diffuse alveolar areas (red arrow) of vehicle group, which is absent in other drug-treated groups. N-positive cells per 50× field per hamster lung section. (E) Representative images of H&E-stained lung tissue section from hamsters treated as indicated, followed by semi-quantitation of histology scores given to each lung tissue by grading the severity of damage in bronchioles, alveoli and blood vessels and accumulating the total scores. Scale bars, 200 μm. One-way ANOVA followed by Dunnett’s post test and compared with vehicle control. ****P < 0.0001, ***P < 0.001. (F–I) F0213 protects mouse from lethal MERS-CoV challenge. (F) Therapeutic treatment used intraperitoneal (IP) administration of F0213 (20 mg/kg), given at 6 hpi, 24 hpi and 48 hpi after virus challenge at day 0. Lung tissue samples were collected at 3 dpi. GS-441524 (40 mg/kg) was included as a control via IP route. Vehicle contains 2% DMSO in 12% SBE-β-CD and by IP injection. (G) Survival and clinical disease were monitored for 14 days or until death. *P < 0.05 by log-rank (Mantel-Cox) tests. (H) Daily body weights of surviving mice. (I) Lung tissues were collected for detection of viral titers at 3 dpi. A value of 30 PFU/mL was assigned for any titer below the 50 PFU/mL detection limit (the dotted line). One-way ANOVA when compared with the vehicle group. *P < 0.05 and **P < 0.01