Fig. 4: NTZ inhibition of PRRSV shedding and transmission.
From: High-throughput screening unveils nitazoxanide as a potent PRRSV inhibitor by targeting NMRAL1
a Viral load in blood, and shedding in oronasal and anal swabs. Viral load or shedding in blood and oronasal swabs were quantified from 2 to 4 dpi, and in anal swabs from 2 to 5 dpi. Viral copy numbers for each pig during this period are presented. b NTZ suppression of PRRSV proliferation in blood. 48 h post infection (infected with 1 × 105.5 TCID50 of GSWW-18 strain), pigs were orally administered NTZ at 10 mg/kg or 5 mg/kg at 0 h and 12 h, followed by blood collection via anterior vena cava or ear marginal vein. Data were normalized to highest and lowest values and fitted with LOWESS curves; semi-transparent lines represent pre-fitting data for each group. c Experimental design for NTZ reduction of PRRSV transmission. NTZ oral administration commenced simultaneously with infection (1 × 105.5 TCID50 of GSWW-18 strain) at 0 dpi, with daily collection of oronasal and anal swabs for 14 days, and all animals euthanized on day 14 for tissue and BALF collection. In the Mock co-house group, three animals survived until 14 dpi. d Viral loads in tissues of all experimental animals at 14 days. e Viral loads in BALF and shedding in oronasal and anal swabs over 14 days for PRRSV. f Pharmacokinetic curve and selected pharmacokinetic parameters. Parameters were calculated using a non-compartmental analysis (NCA). Eighteen pigs were evenly divided into three dosage groups (n = 6), each housed separately, fasted for 12 h before the experiment, and monitored by professional veterinarians for welfare and enclosure cleaning to prevent coprophagia. g Tissue distribution of NTZ’s main metabolite TIZ. Tissues were collected as per Method Pharmacokinetics and Tissue Distribution of NTZ, quantifying TIZ content at various times (n = 2). Each bar represents an individual pig, with colors corresponding to the groups in Fig 4c and dashed lines represent the limit of detection (d, e). Symbols represent three or six independent biological replicates (a, b, f) Scatter plots (a, f) show mean ± SD values of samples, with P-values as indicated, calculated via two-way ANOVA with Dunnett’s multiple-comparison test (a), P-values < 0.0332 were considered significant.
