3.2  Inhibiting virus adsorption and invasion
The first step for virus to invade a cell is to bind to the cell surface by electrostatic interaction or a receptor, such as heparan sulfated proteoglycan on the cell surface. Polysaccharides, especially sulfated polysaccharides, have strong polyanionic properties, and can block the positive charge on the cell surface to prevent virus adsorption or invasion [12]. The invasion process of virus is often associated with the endocytosis of virus, the fusion of virus with cell membrane, and the translocation of virus [12]. Heparin or heparin-like materials with broad-spectrum antiviral properties [[87], [88], [89]] have been developed to mimic the cell surface carbohydrates responsible for initial viral attachment, such as HS and carrageenan [34,90]. The sulfated polysaccharide derived from marine microalga showed strong inhibition against IAV infection via the viral adsorption and internalization steps [91]. The antiviral effect of sulfated polysaccharides from seaweeds was mainly exerted during dengue virus (DENV)-2 adsorption and internalization [92]. Iota-carrageenan and its N-sulfonated derivatives of poly (allylamine) hydrochloride showed strong antiviral activities against human metapneumovirus (hMPV), a kind of respiratory infections RNA virus, by blocking virus release from the cellular membrane and inhibiting virus adsorption [93]. Iota-carrageenan also effectively prevents the replication of HRV in primary human nasal epithelial cells in culture. The data suggest that iota-carrageenan acts primarily by preventing the binding or the entry of virions into the cells [85]. Fucoidan can bind to the neuraminidase (NA) of IAV, and inhibit the activity of NA to block the release of IAV. Additionally, fucoidan can also interfere with the activation of EGFR, PKCα, NF-κB, and Akt, and inhibit both IAV endocytosis and EGFR internalization in IAV-infected cells [73]. The antiviral mechanism of the fucoidans may be through blocking herpes simplex virus (HSV)-2 virion adsorption to host cells [94]. Our team found that 3,6-O-sulfated chitosan (36S) possessed broad anti-HPV activities by directly targeting viral capsid protein and host PI3K/Akt/mTOR pathway to inhibit cell autophagy (Fig. 6 ) [95]. Interestingly, using HCoV-NL63 as a model system, it can be determined that HTCC polymer blocks the interaction between S protein and cell receptor, consequently blocking its entry into cells and preventing virus infection [68,96]. The nano/microspheres of N-(2-hydroxypropyl) -3-trimethyl chitosan (HTCC-NS/MS) were used for adsorption of the coronavirus HCoV-NL63 from aqueous virus suspensions. This nano/microspheres can be applied for the removal of coronaviruses and purification of water from pathogenic coronaviruses [97].
Fig. 6 The mechanism of 3,6-O-sulfated chitosan inhibiting HBV [95].