Table Legends
Table 1 Nitazoxanide input parameters for the PBPK model
Table 2 Tizoxanide validation against observed data for various single oral doses in the fasted state
Table 3 Tizoxanide validation against observed data for various single and multiple oral doses when given with food

Table S1 Legend

Table S1 Nitazoxanide 50% and 90 % effective concentrations against various influenza virus strains

Figure S1 Legend

Figure S1 Comparison of simulated and observed plasma concentration–time curve of tizoxanide (TIZ) at fasted state. (a ) 500 mg, (b ) 1000 mg, (c ) 2000 mg, (d ) 3000 mg and (e ) 4000 mg.

Figure S2 Legend

Figure S2 Comparison of simulated and observed plasma concentration–time curve of tizoxanide (TIZ) for single and multiple dosing regimen (where available) at fed state. (a ) 500 mg, (b ) 1000 mg, (c ) 2000 mg, (d ) 3000 mg and (e ) 4000 mg

Figure S3 Legend

Figure S3 Predicted plasma and lung concentrations for optimal doses during fasted state at different regimens reaching steady state – (a ) 2900 mg BID, (b ) 1600 mg TID and (c ) 1200 mg QID. TIZ – tizoxanide, SD – standard deviation, solid red line indicates clinical Cmax of 1 g single dose at fasted state [29], solid green line represents clinical Cmax of 500 mg single dose [55] at fasted state and the dotted red line represents the EC90 of nitazoxanide for SARS-CoV-2 [44].