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Volume 5, Issue 3 (Suppl)
J Infect Dis Ther, an open access journal
ISSN:2332-0877
Infectious Diseases 2017
August 21-23, 2017
3
rd
Annual Congress on
Infectious Diseases
August 21-23, 2017 San Francisco, USA
A novel small-molecule inhibitor of influenza A virus that acts by disrupting PB2 cap-binding of
the viral polymerase
Yuan Shuofeng
The University of Hong Kong, Hong Kong
T
he conserved residues 318-483 in PB2 subunit (PB2
cap
) of influenza A polymerase is an independently folded cap-binding
domain that exhibits a distinct binding mode from the cap-binding proteins of host cells, thus it is conceived to be a
potential target for the development of new antiviral drugs. We developed an innovative fluorescence polarization assay
to identify small-molecule inhibitors that specifically disrupted the interaction between a cap analog (m
7
GTP) and PB2
cap
.
Selected compounds were tested
in vitro
and in vivo for antiviral efficacy. Of these, the best compound PB2-19 was identified
as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7,
H7N9 and H9N2, in Madin-Darby canine kidney cell cultures. Combinational treatment of zanamivir and PB2-19 exerted
synergistic anti-influenza effect
in vitro
. Intranasal administration of PB2-19 enhanced survival rate and reduced lung viral
loads in BALB/c mice challenged with lethal dose of H1N1 virus. Docking analyses predicted the compound interacted with
the PB2 cap-binding pocket in a similar manner as m7GTP, suggesting its role as a cap-binding competitor. Our study provides
new insights for the development of a new category of influenza therapeutic agents that directly target to PB2 cap-binding
domain.
Biography
Yuan Shuofeng has strong experience in Virology. He did his PhD degree from the University of Hong Kong, studying the anti-influenza drugs development. He has
joined HKU Department of Microbiology as a Post-doctoral Fellow since 2015. He has extensive experiences in establishment of drug screening system and animal
models. He has also published several papers on the development of antiviral agents that target on the polymerase subunits of influenza virus.
yuansf@hku.hkYuan Shuofeng, J Infect Dis Ther 2017, 5:3 (Suppl)
DOI: 10.4172/2332-0877-C1-027