Table 1.
Therapeutic approaches against norovirus infection.
| Antiviral Approach | Molecule/Formulation |
|---|---|
| Targeting virus binding to host cell surface | • Carbohydrate analogs with structures resembling fucose (citrate and other glucomimetics, milk oligosaccharides). • Heparan sulfate analogs (heparin and suramin). • Soluble histones. • Tannic acid (Chinese herbs). • HBGA-blocking monoclonal antibodies. |
| Targeting the virus-encoded cysteine protease, 3CLpro | • Peptidyl TS inhibitors (aldehyde, α-ketoamide, or α-ketoheterocycle moiety as war head). • Latent TS inhibitors (bisulfite adducts). • TS mimics (α-hydroxyphosphonates and α-hydroxyesters). • Macrocyclic peptide inhibitors. • 3C protease inhibitors possessing a Michael acceptor (Rupintrivir). |
| Targeting the virus-encoded RNA-dependent RNA polymerase | • Nucleoside analogs (Ribavirin, Favipiravir and 2'-C-methyl-cytidine). • Non-nucleoside analog (Suramin and NF023). |
| Other approaches targeting the virus/viral replication | • Heterocyclic carboxamide derivatives. • Cyclosulfamide- and acyclic sulfamide derivatives. • Synthetic (E)-2-styrylchromones. • Piperazine derivatives. • Hippuristanol. • NTPase (NS3) inhibitors. • Peptide-conjugated phosphorodiamidatemorpholine oligomers. • siRNA. |
| Targeting host cell factors/pathways crucial to virus replication | • Inhibitors of virus RNA-interacting host proteins. • Cellular deubiquitinase inhibitors (WP1130 and 2-Cyano-3-Acrylamide Compound-6). • hsp90 inhibitors. • Inhibitors of cholesterol pathways (ACAT inhibitors). |
| Passive immunotherapies | • Oral human immunoglobulins. • Egg yolk antibodies. • Conventional monoclonal antibodies. • Recombinant monoclonal llama-derived nanobodies. |
| Nanoparticles | • Silver nanoparticles. • Gold/Copper Sulfide Core/Shell Nanoparticles. • Copper iodide nanoparticles. |
| Natural phytochemicals and other biological substances | • Flavonoids (black raspberries, cranberries, grape seeds, green tea extracts, mulberries, persimmons and pomegranates). • Catechins (grape seeds and green tea). • Polymeric tannins (berries and persimmons). • Anthocyanidins and polyphenols (Black berries, cranberries, mulberries and pomegranates). • Saponins (red ginseng). • Chitosan (chitins from crustacean exoskeleton). • Oregano oil. • Citric acid. |
| Probiotics | • Bifidobacterium adolescentis • Lactococcus lactis • Lactobacillus paracasei |
| Others | • Nitazoxanide (Drug under clinical development, limited data available on antiviral actions). • HBGAs incorporated hydrogels. • Bismuth subsalicylate. |
ACAT, acyl-CoA:cholesterol acyltransferase; HBGA,histo-blood group antigen; hsp90, heat shock protein 90; siRNA, small interfering RNA; TS, transition state.