Abstract
Development of novel anti-influenza A virus (IAV) drugs with high efficiency and low toxicity is critical for preparedness against influenza outbreaks. Herein, we investigated the anti-IAV activities and mechanisms of fucoidan in vitro and in vivo. The results showed that a fucoidan KW derived from brown algae Kjellmaniella crassifolia effectively blocked IAV infection in vitro with low toxicity. KW possessed broad anti-IAV spectrum and low tendency of induction of viral resistance, superior to the anti-IAV drug amantadine. KW was capable of inactivating virus particles before infection and blocked some stages after adsorption. KW could bind to viral neuraminidase (NA) and inhibit the activity of NA to block the release of IAV. KW also interfered with the activation of EGFR, PKCα, NF-κB, and Akt, and inhibited both IAV endocytosis and EGFR internalization in IAV-infected cells, suggesting that KW may also inhibit cellular EGFR pathway. Moreover, intranasal administration of KW markedly improved survival and decreased viral titers in IAV-infected mice. Therefore, fucoidan KW has the potential to be developed into a novel nasal drop or spray for prevention and treatment of influenza in the future.
Highlights
Fucoidan, a sulfated polysaccharide found mainly in brown algae, was reported to possess a variety of biological activities, including anti-coagulant[10], anti-viral[11,12,13,14], anti-tumor[15], and anti-inflammatory effects[16]
The results showed that the fucoidan KW derived from brown algae Kjellmaniella crassifolia possessed broad anti-influenza A virus (IAV) spectrum and low tendency of induction of viral resistance
The structure of KW was determined by nuclear magnetic resonance spectroscopy (NMR) and electrospray ionization mass spectrometry (ESI-MS) analysis, which showed that KW is a 3-linked 2,4-O-disulfated fucooligosaccharide branched glucuronomannan (Fig. 1A)[23]
Summary
A sulfated polysaccharide found mainly in brown algae, was reported to possess a variety of biological activities, including anti-coagulant[10], anti-viral[11,12,13,14], anti-tumor[15], and anti-inflammatory effects[16]. Hayashi et al reported that a fucoidan isolated from Undaria pinnatifida possessed anti-IAV activities in mice with normal and compromised immunity[18]. Fucoidans could be used as vaccine adjuvants to activate spleen cells and enhance antigen-specific antibody production in mice[20]. Fucoidans have the potential to be developed into novel anti-IAV agents in the future. The results showed that the fucoidan KW derived from brown algae Kjellmaniella crassifolia possessed broad anti-IAV spectrum and low tendency of induction of viral resistance. KW may possibly block IAV invasion and release process by targeting viral neuraminidase and cellular EGFR pathway
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