Fig. 2: Inhibition of FXR reduces ACE2 expression and SARS-CoV-2 infection in vivo.
From: FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
a, Schematic of the experiment performed in Syrian golden hamsters. Sentinel hamsters were not directly inoculated with virus. SARS-CoV-2 infection in sentinel hamsters was achieved through transmission from directly inoculated hamsters after co-housing. b, qPCR showing that treatment with UDCA reduces the levels of ACE2 in hamster nasal turbinates and lungs. Housekeeping gene, Gapdh; n = 5 vehicle (no UDCA) group versus n = 3 UDCA group; unpaired two-tailed t-test; centre line, median; box, interquartile range; whiskers, range; bars, s.d. c, Immunofluorescence images showing the levels of ACE2 in nasal and respiratory epithelium of hamsters receiving UDCA versus vehicle. n = 3 hamsters per group. Scale bars, 100 μm. d, qPCR showing the levels of SARS-CoV-2 RNA in swabs, nasal turbinates and lungs of directly inoculated hamsters and sentinel hamsters treated with UDCA or vehicle and co-housed with infected hamsters. Samples were collected after four days of co-housing. SARS-CoV-2 nucleocapsid RNA quantification relative to 18s rRNA. n = 3 hamsters per group; n = 9 UDCA, n = 6 vehicle hamsters; hamsters from each experiment are represented with different symbols; Kruskal–Wallis test adjusted for multiple comparisons. e, Kaplan–Meier curve showing the percentage of hamsters with a PCR-positive swab for SARS-CoV-2 over the course of the experiment outlined in a. n = 9 UDCA, n = 6 vehicle, n = 5 directly inoculated hamsters; log-rank Mantel–Cox test comparing UDCA versus vehicle. f, Percentage weight change from the start of the experiment outlined in a. Bars, range. Day 0 corresponds to the start of co-housing. g, Percentage weight change after SARS-CoV-2 infection in sentinel hamsters. The time of infection was defined as the earliest day on which a sentinel hamster had a positive swab (day 3 for both UDCA and vehicle groups). n = 3 independent experiments; n = 9 UDCA, n = 6 vehicle, n = 5 directly inoculated hamsters; unpaired two-tailed t-test; centre line, median; box, interquartile range; whiskers, range; bars, s.d.
