Table 5.

The overview of polysaccharides with anti-HSV activity.

Compound	Antiherpetic and Cytotoxicity Assays, Strains, Cells, and Reference Agents	Results	Additional Information	Source
PSP-B2 polysaccharide from Prunellae Spica (Prunella vulgaris L.)	Vero cells, HSV-1, HSV-2 PRA ACV HSV-1 IC50 0.78 µM, HSV-2 1.32 μM	HSV-1 IC50 69 μg/mL HSV-2 IC50 49 μg/mL	No cytotoxicity even at 1600 μg/mL	[84]
Eucheuma gelatinae (seaweed) polysaccharide	Vero cells, HSV-1 PRA ACV EC50 HSV-1(strain F), HSV-2 (strain 333), HSV-1 (strain 106), HSV-1 (strain 153), and HSV-1 (strain blue) 0.78, 0.71, 9.60, 21.11, and 23.50 μg/mL, respectively	HSV-1/F, HSV-2/333, HSV-1/106, HSV-1/153, and HSV-1/blue EC50 0.65, 2.12, 1.11, 1.24, and 1.48 μg/mL, respectively	Effect via activity on early HSV-1 infection. Inhibition of viral DNA synthesis.	[85]
Sulfated polysaccharide SP-III from Sargassum latifolium	Vero cells, HSV-1 PRA	SP-III 33% and 81% inhibition at 20 μg/mL and 40 μg/mL, respectively.	Glucuronic acid, mannose, glucose, xylose and fucose.	[86]
Sulfated polysaccharide SP-2a from Sargassum patens (Kütz.) Agardh	Vero cells, HSV-1 (15577 strain, clinical strain, DM2.1 strain-ACV resistant) PRA Determination of extracellular virucidal activity Time of addition experiment Virus adsorption assay	Inhibition of replication of both the acyclovir-sensitive and -resistant strains of HSV-1, in a dose-dependent manner, EC50 1.5–5.3 μg/mL	Fucose, xylose, mannose, glucose, galactose, galactosamine Extracellular virucidal activity only against the ACV-sensitive strains. This compound might inhibit the attachment of the virus to its host cell.	[87]
ST-F polysaccharide from marine brown algae Sargassum trichophyllum	Vero cells, HSV-2 (UW264 strain) PRA Time of addition experiment	Added to the medium during infection and throughout the incubation (Experiment A) or immediately after viral infection (Experiment B), IC50 18 and 410 μg/mL, respectively. SI > 280 and >12 for A and B, respectively.	(Fucose and galactose) The main antiviral target of ST-F might be virus adsorption and/or penetration step(s) on the host cell surface. Low cytotoxicity	[88]
SPs - sulfated polysaccharides from brown sea algae Sargassum fluitans and red sea algae Solieria filiformis	Vero cells, HSV-1 Neutral red dye method ACV EC50 15.4 ± 5.6 μg/mL	S. fluitans EC50 42.8 ± 4.3 μg/mL and S. filiformis EC50 136.0 ± 12 μg/mL Without cytotoxicity (1–200 μg/mL)	The activity observed suggests that the degree of sulfation, molecular weight, and carbohydrate nature of these polysaccharides may affect the activity	[89]
Polysaccharide fractions C1p and C4p from chlorophyta Ulva armoricana	Vero cells, HSV-1 (wild-type strain 17, sensitive to ACV) CPE ACV EC50 0.3 µg/mL	EC50 373.0 ± 20.7 and 320.9 ± 6 µg/mL	Activities correlated to amounts of rhamnose, uronic acids and degree of sulfation.	[90]
Sp-Am polysaccharide from Acanthophora muscoides	Vero cells, HSV-1, HSV-2 CPE	HSV-1 IC50 1.63 μg/mL, SI = 3.5 HSV-2 IC50 3.5 μg/mL, SI = 99.9	Sulfated polysaccharides from marine seaweeds The possible mechanism of the effect - the inhibition of virus adsorption.	[91]
SP-Gb polysaccharide from Gracila riabirdiae		HSV-1 IC50 0.75 μg/mL, SI = 1.25 HSV-2 IC50 82.2 μg/mL, SI = 94.40
SP-Sf polysaccharide from Solieria filiformis		HSV-1 IC50 0.6 μg/mL, SI = 1.6 HSV-2 IC50 74.9 μg/mL, SI = 97.5
PSC polysaccharide from marine seaweed Sphaerococcus coronopifolius	Vero cells, HSV-1 (wild type strain 17, sensitive to ACV) CPE Time of addition assay Virus adsorption assay ACV SI ˃ 500	EC50 4.1 μg/mL, SI = 61	Galactose, 3,6-anhydrogalactose, uronic acids, sulfated The adsorption step of HSV-1 to the host cell possible mechanism of action.	[92]
PBT polysaccharide from marine seaweed Boergeseniella thuyoides		EC50 17.2 μg/mL, SI = 14.5
Sulfated xylogalactofucans and alginic acids from brown algae Laminaria angustata	RC-37 cells, HSV-1 (KOS) PRA Time of addition assay Virus adsorption assay Virucidal assay	IC50 0.21–25 μg/mL, SI ˃ 40 ˃ 3225	Possible inhibiting HSV attachment to cells by direct interaction with viral particles.	[93]
SU1F1 polysaccharide from green algae Enteromorpha compressa	HEp-2 cells, HSV-1 (clinical isolate) PRA Time-of-addition assay Inhibition of adsorption assay Inhibition of penetration assay Virucidal assay Acyclovir IC50 2100 μg/mL, SI = 1.21	IC50 28.25 μg/mL, SI = 35.3	Chemically altered- sulfated ulvan Broad mechanism of action.	[94]
Sulfated fucoidans (S1-S3) from marine brown alga Padina tetrastomatica	Vero cells, HSV-1 (strains F and B2006), HSV-2 (strain MS) PRA Virucidal assay Effect of treatment period on the antiviral activity	HSV-1 and HSV-2 with IC50 in range of 0.30–1.05 μg/mL B2006 S3 IC50 0.6 μg/mL	Active during the virus adsorption period Degree of sulfation affects the activity	[95]
Polysaccharides from brown seaweed Stoechospermum marginatum	Vero cells, HSV-1 (strains F, TK- B2006 and filed strains, syncytial variants arising after selection with a natural carrageenan, syn 13-8 and 14-1), HSV-2 (MS) PRA	HSV-1 (F) EC50 1.15-50 μg/mL, SI = ˃20 ˃ 869 HSV-2 (MS) EC50 0.78 μg/mL, SI= 0.57 ˃50 F3 B2006, Field, 13-8 and 14-1 strains EC50 0.95, 1.52, 4.52 μg/mL, SI ˃1053, ˃658, ˃221, ˃176	Sulfated fucans Active during the virus adsorption period. No direct virucidal activity. No correlation between the antiviral and anticoagulant activity.	[96]
CiWE CiF3 polysaccharides from brown seaweed Cystoseira indica	Vero cells, HSV-1 (strain F), HSV-2 (strain MS) PRA	IC50 values in the range of 0.5–2.8 μg/mL	Sulfated fucans Degree of sulfation affects the activity. No correlation between the antiviral and anticoagulant activity.	[97]
Sulfated polysaccharide (fucoidan) from brown algae Undaria pinnatifida (Mekabu)	Vero cells, HSV-1 (strain HF), HSV-2 (strain UW-268) PRA A) 1 h after the viral infection, B) immediately after infection	HSV-1 IC50 and SI A) 2.5 μg/mL, ˃800; B) 14 μg/mL, ˃140 HSV-2 IC50 and SI A) 2.6 μg/mL, ˃770; B) 5.1 μg/mL, ˃390	Fucose, galactose Other viruses tested.	[98]
Polysaccharides (GiWE and F3) from red seaweed Grateloupia indica	Vero cells, HSV-1 (strain F, TK- B2006 and filed strains, syncytial variants arising after selection with natural carrageenan, syn 13-8 and 14-1), HSV-2 (MS) PRA	HSV-1 (F) IC50 0.27 μg/mL and HSV-2 (MS), IC50 0.31 μg/mL F3 B2006, Field, 13-8 and 14-1 strains EC50 0.89, 0.87, 1.06, 0.81 μg/mL, SI ˃ 1123, ˃1149, ˃943, ˃1234 No direct virucidal activity at 40 μg/mL	Sulfated galactans Degree of sulfation affects the activity. Possible ability to interfere with the replication cycle.	[99]
Polysaccharide from Schizymenia binderi	Vero cells, HSV-1 (strains F, TK− (B2006), (Field)), HSV-2 (G) PRA	EC50 0.21-0.76 μg/mL SI > 1000 for all assays No cytotoxicity at 1000 μg/mL	Sulfated galactan Interference with the initial adsorption of viruses to cells, no virucidal activity at 100 μg/mL.	[100]
Polysaccharide from red seaweed Gigartina skottsbergii	Vero cells, HSV-1 (strains F, TK− (B2006), (Field), clinical isolates 1213 LCR/94, 374 LCR/94 and 1180 BE/94), HSV-2 (G, clinical isolate 244 BE/94) PRA	1C3 HSV-1 (F) and HSV-2 (G) EC50 0.7 and 0.5 µg/mL, respectively, SI ˃ 1408 and ˃2128 1T1 HSV-1 (F) and HSV-2 (G) EC50 0.6 and 0.4 µg/mL, respectively, SI ˃ 1538 and ˃2439 Clinical isolates EC50 0.19–2.18 µg/mL	Carrageenans Lack of anticoagulant activity No virucidal activity, effect on virus adsorption	[101]
Proteoglycan GLPG from Ganoderma lucidum (Agaromycetes)—lingzhi mushroom	Vero cells, HSV-1, HSV-2 CPE Virus yield inhibition assay	HSV-1 and HSV-2 EC50 48 and 56 µg/mL, respectively, SI ˃ 42 and >36 No cytotoxicity at 2000 µg/mL	Proteoglycan GLPG (carbohydrate: protein ratio of 10.4: 1) The antiviral activity may be due to its inhibiting HSV attachment to cells, in addition, its inhibition of viral penetration would augment its antiviral activity.	[102]
Polysaccharide RP from Portulaca oleracea	Vero cells, HSV-2 (UW268 strain) PRA Time-of-addition assay Virus adsorption and penetration assay	A: RP added during infection and throughout the incubation thereafter B: RP added immediately after viral infection. A: EC50 210 µg/mL, SI = 33 B: EC50 320 µg/mL, SI = 22	Pectic polysaccharide (RP) Activity against influenza virus tested on MDCK cells.	[103]
Polysaccharide SPLCf from Caesalpinia ferrera	HEp-2 cells, HSV-1 (clinical isolate) PRA Time-of-addition assay Inhibition of adsorption assay Inhibition of penetration Virucidal activity HSV-1 cell to cell spread assay ACV IC50 2100 μg/mL, SI >1.21	IC50 405 μg/mL, SI > 7.4.	Sulfated polysaccharide SPLCf showed the effect on several stages of the HSV replication—virus adsorption, the effect on virus particles and the expression of viral protein.	[104]
Polysaccharides (ANP, AAP) from Acanthopanax sciadophylloides	Vero cells, HSV-2 (UW264 strain) PRA In vivo anti-HSV-2 effects on female BALB/c mice ACV In vivo: Polysaccharides (1 mg/20 μL) or ACV (0.2 mg/20 μL) administered intravaginally twice per day from 3 days before infection to 7 days post-infection.	ANP and AAP IC50 52 and 620 μg/mL when added to the medium during infection and throughout the incubation thereafter HSV-2 IC50 67 and 580 μg/mL when added to the medium immediately after infection.	Acanthopanax sciadophylloides Virus titers in the vaginal region were decreased by the administration of AAP.	[105]
Acidic polysaccharide (nostoflan) from terrestrial cyanobacterium Nostoc flagelliforme	Vero cells, HSV-1 (HF strain) and HSV-2 (UW268 strain) PRA	A: added during infection and throughout the incubation thereafter B: added immediately after viral infection A: HSV-1 IC50 0.37 μg/mL, SI = 13000 A: HSV-2 IC50 2.9 μg/mL, SI = 2700 B: HSV-1 IC50 ˃100 μg/mL, SI = <49 B: HSV-2 IC50 7.7 μg/mL, SI = 1000	Other antiviral activity tested. No anti-thrombin activity.	[106]
Polysaccharide sulfate fraction from Caulerpa racemosa	Vero cells, HSV-1 strain F, TK- B2006 and field strains), HSV-2 G strain) PRA	HSV-1 (strain F, TK- B2006 and field strains) EC50 4.2, 2.4, 2.2 µg/mL, SI ˃ 238, ˃417, ˃454 HSV-2 (strain G) EC50 3.0 µg/mL, SI ˃ 333 No cytotoxic effects up to 1000 µg/mL	Galactose, glucose, arabinose, and xylose as the major components.	[107]