title: Inhibition of Influenza A Virus Infection by Fucoidan Targeting Viral Neuraminidase and Cellular EGFR Pathway.
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.
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, 266003, P.R. China.|Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, 266003, P.R. China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, P. R. China.
authors.forename: Xiaoshuang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University Medical College, Qingdao, 266003, P. R. China.
authors.forename: Cui
authors.initials: C
authors.lastname: Hao
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, 266003, P.R. China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, P. R. China.
authors.forename: Guangling
authors.initials: G
authors.lastname: Jiao
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, 266003, P.R. China.
authors.forename: Xindi
authors.initials: X
authors.lastname: Shan
authors.affiliation: Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, P. R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Tai
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao, 266003, P.R. China.|Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, 266003, P. R. China.|Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, P. R. China.
authors.forename: Guangli
authors.initials: G
authors.lastname: Yu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral; D004285:Dogs; D024882:Drug Resistance, Viral; D004705:Endocytosis / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D009439:Neuraminidase / Q000378:metabolism*; D009976:Orthomyxoviridae Infections / Q000378:metabolism / Q000821:virology; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D011134:Polysaccharides; C007789:fucoidan; D066246:ErbB Receptors; D009439:Neuraminidase