3.4  Activating host antiviral immunomodulatory system
After the virus invades the host, it will trigger the host's immune response, such as regulating the host NK and macrophages cells, inducing the production of immune cytokines, and indirectly exert antiviral effects by activating innate immunity. Chitosan can enhance antigen-specific immune responses by increasing the induction of regulatory T cells, lung resident T cells, and neutralizing antibodies while reversing Th2-skewed immune responses induced by inactivated respiratory syncytial virus (RSV) vaccine without affecting lung histopathology in mice [13]. The sulphated-carrageenan from red alga showed a strong effect on tobacco mosaic virus (TMV) infection by affecting virus accumulation/infectivity and enhancing locally plant immunity [104]. APS can significantly enhance the immunological function of chicken erythrocytes after infected with infectious bursa disease virus (IBDV) [105]. Additionally, APS can reduce the replication of H9N2 AIV and promote early humoral immune responses in young chickens [17]. LNT can significantly down-regulate the expression level of TNF-α, IL-2 and IL-11, and up-modulate the expression levels of IFN-1 and IFN-γ after challenging with infectious hematopoietic necrosis virus (IHNV), which is an RNA virus. The results indicate that the inhibitory effects of LNT on IHNV infection are possibly attributed to its regulation of the innate immune responses and specific immunity [51].
In addition, our team found that PGS, a sulfated derivative of alginate, can effectively inhibit the expression and secretion of HBsAg and HBeAg in HepG2.2.15cells. The anti-HBV mechanism of PGS may be associated with appropriate activation of NF-κB and Raf/MEK/ERK signaling pathways to enhance the interferon system, and interfere with HBV transcription (Fig. 7 ). This study suggested that PGS merits further investigation as a novel anti-HBV agent aimed at modulating the host innate immune system in the future [42]. These studies bring new ideas to the development of current anti-novel coronavirus drugs.
Fig. 7 The molecular mechanisms of PGS inhibits HBV replication. Cellular NF-κB and Raf/MEK/ERK signaling pathways are associated with the activation of innate immune system such as interferon system. PGS can bind and enter into HepG2.2.15 cells to activate the NF-κB and Raf/MEK/ERK pathways to enhance the interferon system, and indirectly suppress HBV transcription [42].