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About:
Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein
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Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
has title
Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein
Creator
Zhang, Hui
Chen, Jingliang
Huang, Feng
Li, Qianwen
Liang, Juanran
Lu, Gen
Lu, Gui
Luo, Baohong
Luo, Yongjie
Pan, Ting
Tan, Likai
Zhang, Junsong
Source
PMC
abstract
Although antiviral drugs are available for the treatment of influenza infection, it is an urgent requirement to develop new antiviral drugs regarding the emergence of drug‐resistant viruses. The nucleoprotein (NP) is conserved among all influenza A viruses (IAVs) and has no cellular equivalent. Therefore, NP is an ideal target for the development of new IAV inhibitors. In this study, we identified a novel anti‐influenza compound, ZBMD‐1, from a library of 20,000 compounds using cell‐based influenza A infection assays. We found that ZBMD‐1 inhibited the replication of H1N1 and H3N2 influenza A virus strains in vitro, with an IC (50) ranging from 0.41–1.14 μM. Furthermore, ZBMD‐1 inhibited the polymerase activity and specifically impaired the nuclear export of NP. Further investigation indicated that ZBMD‐1 binds to the nuclear export signal 3 (NES3) domain and the dimer interface of the NP pocket. ZBMD‐1 also protected mice that were challenged with lethal doses of A/PR/8/1934 (H1N1) virus, effectively relieving lung histopathology changes, as well as strongly inhibiting the expression of pro‐inflammatory cytokines/chemokines, without inducing toxicity effects in mice. These results suggest that ZBMD‐1 is a promising anti‐influenza compound which can be further investigated as a useful strategy against IAVs in the future.
has issue date
2017-11-30
(
xsd:dateTime
)
bibo:doi
10.1111/jcmm.13467
bibo:pmid
29193684
has license
cc-by
sha1sum (hex)
693a08804a5da83a38bff8f67201eb50817e557e
schema:url
https://doi.org/10.1111/jcmm.13467
resource representing a document's title
Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein
has PubMed Central identifier
PMC5824420
has PubMed identifier
29193684
schema:publication
J Cell Mol Med
resource representing a document's body
covid:693a08804a5da83a38bff8f67201eb50817e557e#body_text
is
schema:about
of
named entity 'promising'
named entity 'replication'
named entity 'library'
named entity 'influenza A virus'
named entity 'COMPOUND'
named entity 'INHIBITED'
covid:arg/693a08804a5da83a38bff8f67201eb50817e557e
named entity 'USEFUL'
named entity 'REPLICATION'
named entity 'FOUND'
named entity 'LIBRARY'
named entity 'TARGET'
named entity 'LUNG'
named entity 'INFLAMMATORY'
named entity 'RESISTANT'
named entity 'CELL'
named entity 'VIRUSES'
named entity 'STRATEGY'
named entity 'STUDY'
named entity 'PRO-'
named entity 'AVAILABLE'
named entity 'DOMAIN'
named entity 'LETHAL'
named entity 'URGENT'
named entity 'IMPAIRED'
named entity 'INFLUENZA A'
named entity 'EMERGENCE'
named entity 'TARGETING'
named entity 'INFLUENZA A VIRUS NUCLEOPROTEIN'
named entity 'NOVEL'
named entity 'IDENTIFICATION'
named entity 'DEVELOPMENT'
named entity 'H1N1'
named entity 'EXPRESSION'
named entity 'HISTOPATHOLOGY'
named entity 'POLYMERASE ACTIVITY'
named entity 'DRUG'
named entity 'INTERFACE'
named entity 'NUCLEAR EXPORT'
named entity 'REQUIREMENT'
named entity 'INFLUENZA'
named entity 'RESULTS'
named entity 'CYTOKINES'
named entity 'EQUIVALENT'
named entity 'DIMER'
named entity 'INHIBITORS'
named entity 'BINDS'
named entity 'INHIBITING'
named entity 'SUGGEST'
named entity 'TOXICITY'
named entity 'IN VITRO'
named entity 'STRAINS'
named entity 'ANTIVIRAL DRUGS'
named entity 'DOSES'
named entity 'IS A'
named entity 'COMPOUND'
named entity 'INDUCING'
named entity 'NUCLEOPROTEIN'
named entity 'INFLUENZA INFECTION'
named entity 'NUCLEAR EXPORT'
named entity 'EFFECTS'
named entity 'NOVEL'
named entity 'IDEAL'
named entity 'NUCLEAR EXPORT SIGNAL'
named entity '20%'
named entity 'MICE'
named entity 'USING'
named entity 'H3N2 INFLUENZA'
named entity 'CHANGES'
named entity 'IDENTIFIED'
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