Therapeutic and prevention strategies against human enterovirus 71 infection

Table 1 Natural therapeutic products tested for anti-human enterovirus 71 activity

Natural product (Group)	Tested	Possible mechanism	Advantages	Disadvantages	Ref.
Hydrolysable Ellagitannins	in vitro/in vivo	Inhibit viral absorption/penetration	No obvious side effects	Weak oral activity	[21-30]
Flavonoids	in vitro	Inhibit viral RNA/protein synthesis	Low escape mutants	Mechanism not clear	[18,31–35]
Alkaloids	in vitro/in vivo	Inhibit protein synthesis	No obvious side effects	Mechanism not clear	[36-38]
Deferoxamine	in vitro/in vivo	Upregulation of B cells	Previous US FDA approval for	N/A	[39,40]
			treatment of iron overload

N/A: Not available; US FDA : United States Food and Drug Administration.

Table 2 Synthetic antiviral compounds tested for anti- human enterovirus 71 activity

Synthetic antivirals	Tested	Mechanism	Advantages	Disadvantages	Ref.
Pre-infection
Pleconaril	In vivo	Prevents attachment by binding to viral capsid	High oral availability	Varied capacity of inhibition	[47-49]
BPROZ	In vitro	Prevents attachment by binding to viral capsid	High oral availability	Resistant mutants	[49-54]
Soluble and	In vitro	Prevents attachment	N/A	N/A	[55-57]
anti-SCARB2/PSGL-1
Lactoferrin	In vitro / in vivo	Prevents entry by binding to VP1/ cellular receptor	No obvious side effects (animal)	Mechanism not clear	[58-62]
Suramin	In vitro	Prevents attachment	May inhibit other multiple stages of	Mechanism not clear	[63]
			HEV71 life cycle
Peptides (SP40)	In vitro	Prevents attachment by binding	Small size, high activity/specificity,	Low bioavailability	[64-66]
		to glycosaminoglycans	low toxicity
Post-infection
Rupintrivir	In vitro /in vivo	Inhibits viral 3C protein	Low quantity, low toxicity,	Lack efficacy in natural infection	[67,68]
			high barrier for drug resistace
DTrip-22	In vitro	Inhibits viral 3D polymerase activity	Broad spectrum activity	N/A	[69]
Aurintricarboxylic acid	In vitro	Inhibits viral 3D polymerase activity	N/A	N/A	[76-81]
NITD008	In vitro / in vivo	Inhibits viral 3D polymerase activity	More potent than ribavirin in vivo	May have toxicity issue, resistant mutants	[82,83]
Sorafenib	In vitro	Block virus induced activation of ERK/p38	Licensed for cancer treatment	N/A	[84,85]
		signalling pathways

N/A: Not available.

Table 3 Comparison of human enterovirus 71 vaccine strategies

Vaccines	Tested	Advantages	Disadvantages	Ref.
Live-attenuated vaccine	In vitro / in vivo	Broad spectrum, low cost	Incomplete attenuation	[143-149]
Inactivated vaccine	In vitro / in vivo / clinical trial	Inability to replicate	High cost	[150-162]
Subunit vaccine	In vitro / in vivo	Safe to use	Low immunogenicity	[153,154,163-178]
Synthetic peptides	In vitro / in vivo	Small and safe to use	Low immunogenicity, escape mutants	[94,179-181]
Virus-like particles	In vitro / in vivo	Safe to use	Unstable, need purification, high cost	[162,182-185]
DNA vaccine	In vitro / in vivo	Most resemble native virus, fast production, low cost, can be manipulated	Low neutralising effect	[153,186-190]