Table 3.

Iminosugars have been tested in vivo against a range of INFV strains, with reduced pathology and increased survival in murine lethal infection models achieved.

			Dose
			Response
Iminosugar; INFV	Model	Study size	Control(s)	Reference
6-O-butanoyl-castanospermine (BuCAST)
103–104 PFU A/Puerto Rico/8/34 (H1N1), intranasal	Female BALB/c mice weighing 15–20 g	n = 5/group	200 or 400 mg/kg/d orally BID from 2 h p.i. for 72 h	Tyms & Virogen Ltd (2003)
			200 mg/kg: 20% less increase in lung tissue mass and 2.8-fold reduction in lung PFU 400 mg/kg: 15% less increase in lung tissue mass and 10-fold reduction in lung PFU
			PBS
Homonojirimycin (HNJ)
5 ID50 A/Puerto Rico/8/34 (H1N1), intranasal	Female BALB/c mice weighing 18–22 g	n = 12/group	0.5, 1, and 2 mg/kg orally BID from 2 d pre-challenge, for 6 d	Zhang et al. (2013)
			1 mg/kg: MSD 12.3 ± 1.5 d. 2 mg/kg: MSD 11.7 ± 0.9 d
			Saline: MSD 9.7 ± 3.2 d. 70 mg/kg ribavirin: 70% survival at day 15
		n = 6/group	1 mg/kg orally BID from 2 d pre-challenge, for 6 d
			Significant reduction in lung viral titer at days 4 and 6 p.i.
			Saline. 70 mg/kg ribavirin: significantly reduced lung viral titer
		n = 18/group	1 mg/kg orally BID beginning 2 d pre-challenge, for 6 d
			Increased serum IFN-γ increased at days 4 and 6 p.i., and IL-10 at days 2, 4 and 6 p.i. Reduced serum IL-6 at days 4 and 6 p.i., and TNF-α at days 2, 4, and 6 p.i. Similar effects in lung tissue
			Saline
N-(9-methoxynonyl)-1-deoxynojirimycin (MON-DNJ, UV-4)
1 LD90 mouse-adapted A/Texas/36/91 (H1N1), intranasal	6–8 week old female BALB/c mice	n = 10/group	10 or 100 mg/kg orally from 1 h pre-challenge, and for 7 d p.i. BID or TID	Stavale et al. (2015)
			10 mg/kg: no effect. 100 mg/kg: BID 60% survival; TID 100% survival
			Water: 0% survival
		n = 10/group	10, 20, 40, 60, 80, or 100 mg/kg orally TID from 1 h pre-challenge, for 10 d
			80 mg/kg: 60% survival at day 14. 100 mg/kg (the MED): 100% survival at day 14
			Water: 0% survival. 20 mg/kg oseltamivir phosphate orally BID for 5 d: 100% survival at day 14
		n = 10/group	100 mg/kg orally TID starting at −1, 24, 48, 72, 96, or 120 h relative to challenge, for 7 or 10 d
			Significant protection when given 72–96 hp.i. for 7 or 10 d
			Water: 20% survival. 20 mg/kg oseltamivir phosphate BID for 5 d: protection <120 h p.i.
		n = 5/group	100 mg/kg orally TID from 1 h pre-challenge, for 10 d
			No significant increase in lung tissue mass; lower mean lung viral titer per gram by TCID50 assay at days 2, 4, and 7 p.i.
			Water: increase in lung tissue mass; approximately 1 log higher lung viral titers per gram than treated mice. 20 mg/kg oseltamivir phosphate: similar mass and titers to MON-DNJ-treated mice
		n = 20/group, treated; n = 10/group, control	100 mg/kg orally TID from 1 h pre-challenge, for 10 d
			100% survival; average serum HAI titers were 62, 43, and 174 on days 15, 30, and 120, respectively
			Water: 10% survival; similar HAI titers
1 LD90 mouse-adapted oseltamivir-resistant A/Perth/261/2009 (H1N1), intranasal	6–8 week old female BALB/c mice	n = 10/group	40, 60, 80, 100, 150, or 200 mg/kg orally TID from 1 h pre-challenge, for 10 d
			40 mg/kg: 40% survival. 60 mg/kg: 70% survival. 80, 100, 150, and 200 mg/kg: 100% survival
			Water: 20% survival. 20 mg/kg oseltamivir phosphate BID for 5 d: 10% survival
50 μl 2010/2011 Fluvirin® INFV vaccine, intramuscular, on days 0, 14, and 28	6–8 week old female BALB/c mice	n = 20/group, control; n = 10/group, treated	100 mg/kg orally TID for 10 d post-vaccination
			No effect on serum HAI titer on days 0, 14, 30, and 42
			50 μl PBS intramuscular
1 LD90 mouse-adapted A/California/04/2009 (H1N1), intranasal	6–8 week old female BALB/c mice	n = 10/group, treated; n = 15/group, control	50, 75, 100, or 150 mg/kg orally TID from 1 h pre-challenge, for 10 d	Warfield et al. (2016)
			50 or 150 mg/kg: 80% survival. 75 mg/kg (the MED): 100% survival. 100 mg/kg: 100% survival
			Water: 7% survival. 20 mg/kg oseltamivir phosphate BID for 5 d: 100% survival
1 LD90 mouse-adapted A/New Caledonia/99 (H1N1), intranasal	17 g female BALB/c mice	n = 10/group, treated; n = 14/group, control	50, 75, 100, or 150 mg/kg orally TID from 1 h pre-challenge, for 7 d
			50 mg/kg: 50% survival. 75 mg/kg: 75% survival. 100 mg/kg: 67% survival. 150 mg/kg: 89% survival
			Water: 0% survival. 30 mg/kg oseltamivir phosphate: 78% survival
1 LD90 A/Pennsylvania/10/2010 (H3N2) swine variant, intranasal	17–20 g female BALB/c mice	n = 10/group, treated; n = 14/group, control	50, 75, 100, or 150 mg/kg orally TID from 1 h pre-challenge, for 7 d
			50 mg/kg: 30% survival. 75 mg/kg: 90% survival. 100 mg/kg: 50% survival. 150 mg/kg: 70% survival
			Water: 7% survival. 20 mg/kg oseltamivir phosphate BID for 5 d: 50% survival
1 LD90 B/Sichuan/379/99, intranasal	18 g female BALB/c mice	n = 10/group, treated; n = 15/group, control	50, 75, 100, or 150 mg/kg orally TID from 1 h pre-challenge, for 10 d
			50 mg/kg: 0% survival. 75 mg/kg: 20% survival. 100 mg/kg: 50% survival. 150 mg/kg (the MED): 100% survival
			Water TID for 8 d: 0% survival. 10 mg/kg oseltamivir phosphate TID for 8 d: 100% survival
N-8′-(2′′-tetrahydrofuranyl)-octyl-deoxynojirimycin (2THO-DNJ, UV-12)
1 LD90 mouse-adapted A/Texas/36/91 (H1N1), intranasal	6–8 week old female BALB/c mice	n = 10/group	20, 40, 60, 80, or 100 mg/kg orally TID from 1 h pre-challenge, for 10 d	Warfield et al. (2015)
			20 mg/kg: 0% survival. 40 mg/kg: 50% survival at day 14. 60–80 mg/kg: 90% survival at day 14. 100 mg/kg (the MED): 100% survival at day 14
			Water: 0% survival
		n = 10/group	100 mg/kg orally TID starting at −1, 24, 48, or 72 h relative to challenge, for 10 d
			1 h relative to challenge: 100% survival. 24 h p.i.: 70% survival. 48–72 h p.i.: 0% survival
			Water: 0% survival
		n = 10/group	60 mg/kg orally TID starting at -1, 24, 48, or 72 h relative to challenge, for 10 d
			−1 h relative to challenge: 80% survival. 24 h p.i: 60% survival. 48 h p.i.: 80% survival. 72 h p.i.: 40% survival
			Water: 0% survival

BID: bis in die (twice daily); HAI: hemagglutination inhibition; ID₅₀: dose that is infectious in 50% cases; LD₉₀: lethal dose in 90% cases; MED: minimum effective dose that is 100% protective; MSD: mean survival days; PBS: phosphate buffered saline; PFU: plaque forming units; p.i.: post infection; TCID₅₀: amount of pathogen inducing pathological change in 50% inoculated cell cultures; TID: ter in die (thrice daily).