Journal: Journal of Virology

Article Title: Molnupiravir inhibits Bourbon virus infection and disease-associated pathology in mice

doi: 10.1128/jvi.00740-25

Figure Lengend Snippet: Prophylaxis with molnupiravir protects mice from fatal BRBV infection. ( A through C ) Ifnar1 -/- mice were treated with 50, 150, or 500 mg/kg of molnupiravir or vehicle control twice daily per oral gavage for eight days starting 4 h prior to inoculation with 400× MLD 50 of BRBV. Weight change ( A ), clinical score ( B ), and survival rates ( C ) were monitored for 14 days. Values are the means (± standard error of the mean) of the groups. Weight change and clinical scores are analyzed by the one-way ANOVA followed by Dunnett’s multiple comparisons, and survival is analyzed by the log-rank test. ** P < 0.01; **** P < 0.0001. ( D and E ) Ifnar1 -/- mice were treated with 500 mg/kg of molnupiravir for 4 h prior to infection with 100× MLD 50 of BRBV, and infectious virus titer and viral RNA levels at 3 or 6 dpi in different organs were measured by titration and RT-qPCR, respectively. Each data point represents a single mouse ( n = 6 per group), and values are the means (± standard error of the mean) of the groups. Drug and vehicle-treated groups were analyzed by one-way ANOVA followed by Tukey’s post-test. * P < 0.05; ** P < 0.01.

Article Snippet: Thus, we used molnupiravir in the mouse model. Ifnar1 -/- mice received molnupiravir (MedChemExpress; HY-135853/CS-0114880) at 50 mg/kg, 150 mg/kg, or 500 mg/kg in water containing 10% polyethylene glycol (Sigma) and 2.5% Cremophor RH40 (Sigma) or vehicle only twice daily via oral gavage starting 4 h prior to or 24 and 48 h post-challenge with a lethal dose of BRBV.

Techniques: Infection, Control, Virus, Titration, Quantitative RT-PCR

Journal: Journal of Virology

Article Title: Molnupiravir inhibits Bourbon virus infection and disease-associated pathology in mice

doi: 10.1128/jvi.00740-25

Figure Lengend Snippet: Therapeutic administration of molnupiravir protects mice from fatal BRBV infection. ( A through C ) Ifnar1 -/- mice were inoculated with 100× MLD 50 of BRBV (IP) and treated with 500 mg/kg of molnupiravir (orally, twice daily) starting at 1 day (+1 dpi, red closed triangles, n = 7) or 2 days (+2 dpi, red open circles, n = 8) after infection until they fully recovered (reinstate the initial BW). Mice that received water containing 10% polyethylene glycol and 2.5% Cremophor RH40 starting 2 days after inoculation (vehicle +2 dpi) were used as vehicle controls ( n = 11). Weight change ( A ), clinical score ( B ), and survival rates ( C ) were monitored for 14 days. Values are the means (± standard error of the mean) and are analyzed by one-way ANOVA followed by Dunnett’s multiple comparison and survival by the log-rank test. ** P < 0.01; *** P < 0.005.

Article Snippet: Thus, we used molnupiravir in the mouse model. Ifnar1 -/- mice received molnupiravir (MedChemExpress; HY-135853/CS-0114880) at 50 mg/kg, 150 mg/kg, or 500 mg/kg in water containing 10% polyethylene glycol (Sigma) and 2.5% Cremophor RH40 (Sigma) or vehicle only twice daily via oral gavage starting 4 h prior to or 24 and 48 h post-challenge with a lethal dose of BRBV.

Techniques: Infection, Comparison

Journal: Journal of Virology

Article Title: Molnupiravir inhibits Bourbon virus infection and disease-associated pathology in mice

doi: 10.1128/jvi.00740-25

Figure Lengend Snippet: Molnupiravir reduces BRBV-associated pathology in the spleen and liver. Ifnar1 -/- mice were treated with either vehicle or 500 mg/kg of molnupiravir 4 h prior to inoculation with 100× MLD 50 of BRBV. Mice continued to receive 500 mg/kg of molnupiravir (orally, twice daily) until the day of harvest. ( A ) The gross weight of spleens from vehicle- or molnupiravir-treated mice at 6 dpi. ( B and C ) Representative images of hematoxylin and eosin (H&E) staining of spleens from uninfected ( n = 5 per group) or BRBV-infected (3 or 6 dpi, n = 5-6 per group) mice receiving vehicle or molnupiravir treatment ( B ) and scoring of spleen pathology. ( C ) Circled regions show apoptotic bodies and tingible body macrophages with engulfed debris. MZ, marginal zone. Scale bar, 200 µm. ( D and E ) Representative images after H&E staining of livers from the vehicle or drug-treated mice that were uninfected ( n = 5 per group) or BRBV-infected (3 or 6 dpi, n = 6–13 per group) ( D ) and scoring of liver pathology ( E ). Scale bar, 100 mm. In panels A, C, and E, each data point is from a single mouse, and bars represent the means (± standard error of the mean) of the groups. For analysis of spleen weight, spleen histology, and liver histology of drug- and vehicle-treated groups were from 2 to 3 independent experiments and analyzed by one-way ANOVA followed by Šidák’s post-test. * P < 0.05; ** P < 0.01.

Article Snippet: Thus, we used molnupiravir in the mouse model. Ifnar1 -/- mice received molnupiravir (MedChemExpress; HY-135853/CS-0114880) at 50 mg/kg, 150 mg/kg, or 500 mg/kg in water containing 10% polyethylene glycol (Sigma) and 2.5% Cremophor RH40 (Sigma) or vehicle only twice daily via oral gavage starting 4 h prior to or 24 and 48 h post-challenge with a lethal dose of BRBV.

Techniques: Staining, Infection

Journal: Journal of Virology

Article Title: Molnupiravir inhibits Bourbon virus infection and disease-associated pathology in mice

doi: 10.1128/jvi.00740-25

Figure Lengend Snippet: Molnupiravir improves BRBV-associated cytopenia in the spleen and peripheral blood thrombocytopenia . Ifnar1 -/- mice were treated with 500 mg/kg of molnupiravir at 4 h prior to inoculation with 100× MLD 50 of BRBV, and the two-dose per day regimen was continued until day 6. Mouse splenocytes and blood were harvested at 6 dpi and evaluated by flow cytometry. ( A ) Viability of total splenocytes from vehicle- or molnupiravir-treated mice at 6 dpi, as assessed by staining with a viability dye. ( B and C ) Percentages ( B ) and numbers ( C ) of splenic CD4 + and CD8 + T cells. ( D through F ) Percentages ( D ) and numbers of follicular ( E ) and marginal zone (MZ, F ) B cells in the spleen. ( G through J ) Total counts of peripheral blood platelets ( G ), CD4 + T cells ( H ), CD8 + T cells ( I ), and B cells ( J ). Each data point represents a single mouse, and the bars represent the means of the groups. Drug and vehicle-treated groups were analyzed by one-way ANOVA with Šidák’s post-test. * P < 0.05; ** P < 0.01; *** P < 0.005; **** P < 0.005. The data are pooled from two independent experiments ( n = 5–8 per group).

Article Snippet: Thus, we used molnupiravir in the mouse model. Ifnar1 -/- mice received molnupiravir (MedChemExpress; HY-135853/CS-0114880) at 50 mg/kg, 150 mg/kg, or 500 mg/kg in water containing 10% polyethylene glycol (Sigma) and 2.5% Cremophor RH40 (Sigma) or vehicle only twice daily via oral gavage starting 4 h prior to or 24 and 48 h post-challenge with a lethal dose of BRBV.

Techniques: Flow Cytometry, Staining