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. 2021 Jul 26;132(1):41–58. doi: 10.1111/jam.15202

TABLE 1.

Summary of the studies for the investigation of chitosan and chitosan derivatives as antiviral agents

Virus type

Type of Chitosan a

Type of virus host used

Chitosan concentration/dose Antiviral activity ET TºC pH References
BmNPV ODV

The chitosan was prepared from larvae of housefly

Fresh leaves of mulberry—53rd silk worm larva for BmNPV

The Sf9 cells were used for AcMnPV

0.5 mg/ml chitosan The virus titre TCID50/ml declined significantly from 2.0 × 107 to 2.8 × 106 24 h 37 7.4 Ai et al. (2012)
AcMNPV
1.0 mg/ml The virus titre TCID50/ml declined from 2.0 × 107 to 3.3 × 105 1 h 28 7.4
HCMV strain AD169

Chitosan of medium molecular weight (viscosity 200–800 cP, 1% w/v in 1% v/v acetic acid), with a degree of deacetylation of 85%

Human embryonic lung fibroblasts

4.5 mg chitosan/8.8–14 mg Fostcanet antiviral drug used as nanoparticle delivery system IC50 40–58 µM for nanoparticle delivery system compared to free Fostcanet 41 μM. The system maintained the activity of Fostcanet and could be useful in improving blood residence time and prolongation of contact of the drug with CMV‐infected cells. 3–5 days 37 Acid to neut. Russo et al. (2014)
H1N1 Influenza A virus

Chitosan (average molecular weight 54 kg/mol, deacetylation ratio 84%).

Madin–Darby Canine Kidney cells

10 mg/ml chitosan with Ag nanoparticles No antiviral activity was observed for chitosan alone; however, Ag nanoparticles bound to chitosan showed significant antiviral activity 1 h RT 5.2–6.3 Mori et al. (2013)
H7N9

0.4% (w/v) solution of chitosan was prepared in sodium acetate solution at a concentration of 25mmol/L

Mice intranasal dosing

100 μg chitosan dose intranasal route mice The lung virus titres (log TCID50/ml) decreased from 6.63 to 3.38 7 days 37 5.0 Zheng et al. (2016)
RVFV

The degree of deacetylation (DDA) of chitosan was 80.5% dissolved in 0.1 M acetic acid.

Vero cells

60μg/ml chitosan The log cycle difference was 1.6 with reduction of 24.9% 24 h 37 Acid Hassan et al. (2016)
HSV‐1 One log cycle difference and the reduction percent was 18.8%
Coxsackie virus One log cycle difference and the reduction percent was 26.1%
Potato Virus X

Crab chitosan low molecular weight chitosan 2.2 and 1.2 kDa with deacetylation degree of 85%

Leaves of Phaseolus vulgaris L. cultivar Contender bean plant

100 µg/ml chitosan solution was sprayed on leaves Complete suppression of virus infection after applying chitosan on the leaves using enzyme immunoassay test 14 days RT 5.8 Kulikov et al. (2006)
Tobacco Mosaic Virus
Newcastle disease virus

6‐deoxy‐6‐bromo‐N‐phthaloyl chitosan derivative

Virus was inoculated in embryonated chicken SPF eggs

1 g/L chitosan derivative dissolved in physiological saline Reduced the hemagglutination titre of virus to zero 72 h 37 Neut. He et al. (2019)
Tobacco mosaic virus

Guanidine derivatives of chitosan with molecular weight 210 kDa The deacetylation degree was determined as 91.6%

N. glutinos and N. tobacum plants

1 mg/ml chitosan derivative solution used on plants

The inhibitory effect was evaluated using special Light Bioculturer to investigate the local lesions on half leaves

The chitosan derivative resulted in 52% of inhibitory effect

12 h RT 7.2 Hu et al. (2009)
Hepatitis C virus

Curcumin chitosan nanocomposite

Human hepatoma cells Huh7

20 µg/ml of 4% of curcumin encapsulated into chitosan nanocomposite

Real‐time PCR test antiviral activity

High antiviral activity against entry of HCV into Huh7 cells by almost 100%reduction in viral titre

24 h 37 NA Loutfy et al. (2020)
HSV‐1 and HSV‐2

Acyclovir loaded in 1% w/w chitosan in acetic acid (medium MW, deacetylation 75–85%) nanoemulsion

Applied on African green monkey kidney (Vero) cells

The loading capacity of the drug was about 8.5%

Virus yield reduction assay showed IC50 values against HSV‐1 at 48 h was 0.012 µM for acyclovir‐loaded nanoemulsion and 0.156 µM for free acyclovir

IC50 obtained against HSV‐2 determined at 24 h post‐infection were 0.100 µM for acyclovir‐loaded nanoemulsion and 1.608 µM for free acyclovir

24 h 48 h 37 Acid Donalisio et al. (2018)
HIV‐1

Chitosan–zinc stabilized (degree of acetylation (DA)~4%, average molar mass (Mw)~5.8 × 105 g/mol) and chondroitin sulphate polyelectrolyte complex for delivery of Tenofovir

Human peripheral blood mononuclear cells

Chitosan 0.1%–0.2% w/v in acetic acid solution IC50 was decreased from 4.35 µmol/L for aqueous Tenofovir to 1.95 µmol/L for Tenofovir‐loaded polyelectrolyte complex nanoparticles NA 37 4–5.5 Wu et al. (2016)
Feline Infectious Peritonitis virus

20 µM Curcumin loaded in low molecular weight chitosan (75%–85%) deacetylated

CrFK cell culture

Different concentrations of curcumin were added to a fixed concentration of chitosan nanoparticles in ratios of 0.5:1, 0.75:1 and 1:1 Cur‐CS nanoparticles exhibited antiviral effects, with an SI value three times higher than that of curcumin 24 h 48 h 37 3.0 Ng et al. (2020)
Hepatitis A virus

Polyquaternary phosphonium oligochitosans/nanosilver

Vero cells – Hepatitis A virus

Feline calici virus – Crandell Reese feline kidney cells

Coxsackie virus B4‐Hep 2 cell lines

100 μl/ml polyquaternary phosphonium oligochitosans/nanosilver Maximum viral percent reduction was 41.4% 5 days 37 3.0–9.0 Sofy et al. (2019)
Norovirus/Feline calici virus Reduction 80.6%
Coxsackie virus B4 Reduction 84.0%

Abbreviations: AcMNPV, Autographa californica nucleopolyhedrovirus; NA , no available information; ET, exposure time; T°C, Temperature in °C; RT, room temperature; h, hour.

a

Chitosan quality was not fully described in terms of source, molecular weight, degree of deacetylation, purity, percent ash and protein content.