Figure 6.
Effect of pretreatment with BX795 during sequential RV, SARS-CoV-2 infection, and low-MOI SARS-COV-2 infection. (A) Organoid cultures were pretreated with or without BX795 for 18 h, mock infected or infected with HRV-01A, incubated for 3 d, and then infected with SARS-CoV-2 MOI 0.5. BX795 was present throughout the experiment. (B) Effect of BX795 pretreatment on ISG induction 3 d after RV infection. Bars show FC in ISG mRNA level in RV infected cultures compared with mock without (left) or with (right) BX795 pretreatment. Bars shown mean and SEM of four replicates per condition and are representative of three independent experiments using primary cells from different donors. Significant difference in ISG level by Mann–Whitney is indicated (#, P = 0.0303). (C) SARS-CoV-2 viral RNA level relative to the limit of detection in organoid cultures 72 h after SARS-CoV-2 infection, with and without BX795 and/or RV pretreatment. (D) HRV-01A viral RNA level relative to the limit of detection in organoid cultures 72 h after SARS-CoV-2 infection, with and without BX795 and/or RV pretreatment. This graph also includes cultures infected with RV, but not subsequently infected with SARS-CoV-2. (E) Cultures were pretreated with 6 µM BX795 or medium only for 18 h and then inoculated with SARS-CoV-2, MOI 0.05, at t = 0 (F–H). (F) SARS-CoV-2 viral RNA level relative to the limit of detection in organoid cultures 72 h after infection, with and without BX795 pretreatment (black or white bars, respectively. (G) SARS-CoV-2 viral RNA level relative to the limit of detection in apical wash 72 h after infection, with and without BX795 pretreatment (black or white bars, respectively). (H) Doubling time calculations for SARS-CoV-2 in organoids with and without BX795 pretreatment, assuming exponential growth between 1 and 72 h. Exponential growth curves were compared by the extra sum-of-squares F-test and found to be significantly different (###, P = 0.0011). For C, D, F, and G, bars show mean and SEM of four to six biological replicates per condition. P values indicate significant differences in ISG or viral RNA by Mann–Whitney test (*, P = 0.0449; ##, P = 0.0286; **, P = 0.0095; ***, P = 0.0043; ****, P < 0.0001). Data are representative of two independent experiments using primary cells from different donors.

Effect of pretreatment with BX795 during sequential RV, SARS-CoV-2 infection, and low-MOI SARS-COV-2 infection. (A) Organoid cultures were pretreated with or without BX795 for 18 h, mock infected or infected with HRV-01A, incubated for 3 d, and then infected with SARS-CoV-2 MOI 0.5. BX795 was present throughout the experiment. (B) Effect of BX795 pretreatment on ISG induction 3 d after RV infection. Bars show FC in ISG mRNA level in RV infected cultures compared with mock without (left) or with (right) BX795 pretreatment. Bars shown mean and SEM of four replicates per condition and are representative of three independent experiments using primary cells from different donors. Significant difference in ISG level by Mann–Whitney is indicated (#, P = 0.0303). (C) SARS-CoV-2 viral RNA level relative to the limit of detection in organoid cultures 72 h after SARS-CoV-2 infection, with and without BX795 and/or RV pretreatment. (D) HRV-01A viral RNA level relative to the limit of detection in organoid cultures 72 h after SARS-CoV-2 infection, with and without BX795 and/or RV pretreatment. This graph also includes cultures infected with RV, but not subsequently infected with SARS-CoV-2. (E) Cultures were pretreated with 6 µM BX795 or medium only for 18 h and then inoculated with SARS-CoV-2, MOI 0.05, at t = 0 (F–H). (F) SARS-CoV-2 viral RNA level relative to the limit of detection in organoid cultures 72 h after infection, with and without BX795 pretreatment (black or white bars, respectively. (G) SARS-CoV-2 viral RNA level relative to the limit of detection in apical wash 72 h after infection, with and without BX795 pretreatment (black or white bars, respectively). (H) Doubling time calculations for SARS-CoV-2 in organoids with and without BX795 pretreatment, assuming exponential growth between 1 and 72 h. Exponential growth curves were compared by the extra sum-of-squares F-test and found to be significantly different (###, P = 0.0011). For C, D, F, and G, bars show mean and SEM of four to six biological replicates per condition. P values indicate significant differences in ISG or viral RNA by Mann–Whitney test (*, P = 0.0449; ##, P = 0.0286; **, P = 0.0095; ***, P = 0.0043; ****, P < 0.0001). Data are representative of two independent experiments using primary cells from different donors.

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