Fig. 5: Therapeutic postexposure administration of ISM3312 against SARS-CoV-2 variants and various human coronaviruses in vivo. | Nature Communications

Fig. 5: Therapeutic postexposure administration of ISM3312 against SARS-CoV-2 variants and various human coronaviruses in vivo.

From: A novel, covalent broad-spectrum inhibitor targeting human coronavirus Mpro

Fig. 5: Therapeutic postexposure administration of ISM3312 against SARS-CoV-2 variants and various human coronaviruses in vivo.

a Weight loss and survival curve of Nirmatrelvir and ISM3312 against ancestral SARS-CoV-2 using H11-K18-hACE2 C57BL/6 mice (Mock, n = 4 mice; other groups, n = 8 mice). Virus titers in ancestral SARS-CoV-2 infected lungs (dpi 1) and brains (dpi 3) were quantified by FFA (Mock, n = 4 mice; other groups, n = 8 mice). b Weight loss and survival curve of Nirmatrelvir and ISM3312 against SARS-CoV-2 BA.2.3 using H11-K18-hACE2 C57BL/6 mice (n = 8 mice). Virus titers in the SARS-CoV-2 BA.2.3 infected lungs (dpi 1) and brains (dpi 4) were quantified by FFA (Mock, n = 4 mice; other groups, n = 8 mice). c Virus titers in the SARS-CoV-2 XBB.1 infected lungs (dpi 1) and brains (dpi 4) were quantified by FFA (n = 5 mice). d. Weight loss and survival curve of ISM3312 against MERS-CoV mouse adapted virus MA30 using hDPP4 knockin C57BL/6 mice (n = 6 mice). Viral titers in MERS-CoV MA30 infected lungs were quantified by FFA (n = 4–5 mice). e Viral gene copy number in 229E infected lungs from hAPN KI BALB/c mice were quantified by qRT–PCR (n = 5 mice). f Viral gene copy number in NL63 infected lungs from Ad5-hACE2 sensitized IFNARKO BALB/c mice were quantified by qRT–PCR (n = 4–5 mice). g. Weight loss and survival curve of ISM3312 against OC43 using WT C57BL/6 mice (n = 5–6 mice). Viral gene copy numbers in the OC43 infected brains and spinal cords at 5 dpi were quantified by qRT–PCR (n = 4 mice). Data were analyzed by using one-way ANOVA (a, c) or two-way ANOVA followed by Tukey’s multiple comparisons test (d, g). Two-sided unpaired t-tests were performed in e and f with Welch’s correction in e (data of Dpi 3). Data are presented as mean values ± SEM. Exact P values are reported in the figure. Source data are provided as a Source Data file.

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