Fig. 4: 4H30 could broadly inhibit SARS-CoV-2 variants in hamsters.

a, b Histopathology of hamster lungs (a) and body weight of hamsters (b) treated by 4H30 or PBS. Three intranasal doses of 4H30 (0.5 mg/kg) were administered within two days. The lung tissues were harvested on day 4 post-inoculation for H&E staining. Scale bar, 100 μm. c 4H30 showed pre-exposure activity to significantly inhibit SARS-CoV-2 (B.1.1.63) replication. Intranasal 4H30 (0.5 mg/kg) was administered to hamsters at 24 h (n = 4), 8 h (n = 4), 4 h (n = 6), or before virus challenge (4H30pre, n = 4). Intranasal H23 was administered to hamsters before the virus challenge (H23pre). Virus titers in the lungs were measured at 2 dpi. **P < 0.01 when compared with PBS-treated hamsters (Mock). d 4H30pre could reduce syncytia formation in the bronchial epithelium of hamsters when compared with mock-treated hamsters. White circles indicated the syncytial cells with 4 or more nuclei. Scale bar, 25 μm. e 4H30 showed post-exposure activity to inhibit SARS-CoV-2 (B.1.1.63) replication (n = 4). 4H30 (0.5 or 0.1 mg/kg) or PBS (Mock) was intranasally inoculated into hamsters at 8 hpi. Virus titers were measured at 2 dpi. f 4H30 and remdesivir could significantly inhibit SARS-CoV-2 (B.1.617.2) replication in hamster lungs (n = 4). Intranasal 4H30 or remdesivir (0.5 mg/kg) were administered to hamsters at 8 hpi and two more doses were given to hamsters in the following day. Virus titers were measured at 2 dpi. **P < 0.01 when compared with Mock-treated hamsters. g 4H30 could reduce syncytia formation in the bronchial epithelium of hamsters challenged by the SARS-CoV-2 Delta variant (B.1.617.2). Representative images were taken at 2 dpi. Scale bar, 25 μm. h–j Anti-Delta activity at 3 dpi. Infected hamsters were intranasally inoculated with PBS (Mock, n = 4), 4H30 (n = 3), remdesivir (n = 3) or 4H30 + Cam (n = 3, camostat = 1 mg/kg) at 8 hpi. Viral titers (h), body weight (i), and histopathology (j) were tested at 3 dpi. *P < 0.05 and **P < 0.01 when compared with Mock. Scale bar, 25 μm. The red triangle indicated the desquamation of the epithelial cells. White circles indicated the syncytial cells with six or more nuclei. Data were presented as means ± SD of indicated independent biological samples.