Identification of influenza polymerase inhibitors targeting C-terminal domain of PA through surface plasmon resonance screening
Identifieur interne : 000E53 ( Ncbi/Curation ); précédent : 000E52; suivant : 000E54Identification of influenza polymerase inhibitors targeting C-terminal domain of PA through surface plasmon resonance screening
Auteurs : Chun-Yeung Lo ; Olive Tin-Wai Li ; Wen-Ping Tang [République populaire de Chine] ; Chun Hu [République populaire de Chine] ; Guo Xin Wang [République populaire de Chine] ; Jacky Chi-Ki Ngo ; David Chi-Cheong Wan ; Leo Lit-Man Poon ; Pang-Chui ShawSource :
- Scientific Reports [ 2045-2322 ] ; 2018.
Abstract
Currently, many strains of influenza A virus have developed resistance against anti-influenza drugs, and it is essential to find new chemicals to combat this virus. The influenza polymerase with three proteins, PA, PB1 and PB2, is a crucial component of the viral ribonucleoprotein (RNP) complex. Here, we report the identification of a hit compound
Url:
DOI: 10.1038/s41598-018-20772-9
PubMed: 29396435
PubMed Central: 5797126
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<front><div type="abstract" xml:lang="en"><p id="Par1">Currently, many strains of influenza A virus have developed resistance against anti-influenza drugs, and it is essential to find new chemicals to combat this virus. The influenza polymerase with three proteins, PA, PB1 and PB2, is a crucial component of the viral ribonucleoprotein (RNP) complex. Here, we report the identification of a hit compound <bold>221</bold>
by surface plasmon resonance (SPR) direct binding screening on the C-terminal of PA (PAC). Compound 221 can subdue influenza RNP activities and attenuate influenza virus replication. Its analogs were subsequently investigated and twelve of them could attenuate RNP activities. One of the analogs, compound 312, impeded influenza A virus replication in Madin-Darby canine kidney cells with IC<sub>50</sub>
of 27.0 ± 16.8 μM. <italic>In vitro</italic>
interaction assays showed that compound 312 bound directly to PAC with Kd of about 40 μM. Overall, the identification of novel PAC-targeting compounds provides new ground for drug design against influenza virus in the future.</p>
</div>
</front>
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