DAS181 inhibits H5N1 influenza virus infection of human lung tissues.
DAS181 is a novel candidate therapeutic agent against influenza virus which functions via the mechanism of removing the virus receptor, sialic acid (Sia), from the adjacent glycan structures. DAS181 and its analogues have previously been shown to be potently active against multiple strains of seasonal and avian influenza virus strains in several experimental models, including cell lines, mice, and ferrets. Here we demonstrate that DAS181 treatment leads to desialylation of both alpha2-6-linked and alpha2-3-linked Sia in ex vivo human lung tissue culture and primary pneumocytes. DAS181 treatment also effectively protects human lung tissue and pneumocytes against the highly pathogenic avian influenza virus H5N1 (A/Vietnam/3046/2004). Two doses of DAS181 treatment given 12 h apart were sufficient to block H5N1 infection in the ex vivo lung tissue culture. These findings support the potential value of DAS181 as a broad-spectrum therapeutic agent against influenza viruses, especially H5N1.
Chan
Renee W Y
RW
Department of Microbiology, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR.
Chan
Michael C W
MC
Wong
Adam C N
AC
Karamanska
Rositsa
R
Dell
Anne
A
Haslam
Stuart M
SM
Sihoe
Alan D L
AD
Chui
W H
WH
Triana-Baltzer
Gallen
G
Li
Qixiang
Q
Peiris
J S Malik
JS
Fang
Fang
F
Nicholls
John M
JM
D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000821:virology*; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000998:Antiviral Agents; D011134:Polysaccharides; D011993:Recombinant Fusion Proteins; C525612:oplunofusp