title: Edible bird's nest modulate intracellular molecular pathways of influenza A virus infected cells.
abstract: BACKGROUND
  Edible Bird's Nest (EBN) as a popular traditional Chinese medicine is believed to have health enhancing and antiviral activities against influenza A virus (IAV); however, the molecular mechanism behind therapeutic effects of EBN is not well characterized.
  
  
  METHODS
  In this study, EBNs that underwent different enzymatic preparation were tested against IAV infected cells. 50% cytotoxic concentration (CC50) and 50% inhibitory concentration (IC50) of the EBNs against IAV strain A/Puerto Rico/8/1934(H1N1) were determined by HA and MTT assays. Subsequently, the sialic acid content of the used EBNs were analyzed by fluorometric HPLC. Western Blotting and immunofluorescent staining were used to investigate the effects of EBNs on early endosomal trafficking and autophagy process of influenza virus.
  
  
  RESULTS
  This study showed that post inoculations of EBNs after enzymatic preparations have the highest efficacy to inhibit IAV. While CC50 of the tested EBNs ranged from 27.5-32 mg/ml, the IC50 of these compounds ranged between 2.5-4.9 mg/ml. EBNs could inhibit IAV as efficient as commercial antiviral agents, such as amantadine and oseltamivir with different mechanisms of action against IAV. The antiviral activity of these EBNs correlated with the content of N-acetyl neuraminic acid. EBNs could affect early endosomal trafficking of the virus by reducing Rab5 and RhoA GTPase proteins and also reoriented actin cytoskeleton of IAV infected cells. In addition, for the first time this study showed that EBNs can inhibit intracellular autophagy process of IAV life cycle as evidenced by reduction of LC3-II and increasing of lysosomal degradation.
  
  
  CONCLUSIONS
  The results procured in this study support the potential of EBNs as supplementary medication or alternative to antiviral agents to inhibit influenza infections. Evidently, EBNs can be a promising antiviral agent; however, these natural compounds should be screened for their metabolites prior to usage as therapeutic approach.
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.|Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Amin
authors.identifier: http://orcid.org/0000-0002-6052-8793
authors.initials: A
authors.lastname: Haghani
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.|Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Mehrbod
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.|Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Nikoo
authors.initials: N
authors.lastname: Safi
authors.affiliation: Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
authors.forename: Fadzilah A'ini Abd
authors.initials: FA
authors.lastname: Kadir
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.|Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
authors.forename: Abdul Rahman
authors.initials: AR
authors.lastname: Omar
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia. aiini@upm.my.|Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia. aiini@upm.my.
authors.forename: Aini
authors.initials: A
authors.lastname: Ideris
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D001685:Biological Factors / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D001717:Birds / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000502:physiology; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D007251:Influenza, Human / Q000378:metabolism / Q000821:virology*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D001685:Biological Factors; D020696:rab5 GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
keywords: Antiviral; Autophagy; Edible bird nest (EBN); Endosome trafficking; Immunoflourescent; Influenza A virus; Sialic acid