Identification of influenza polymerase inhibitors targeting C-terminal domain of PA through surface plasmon resonance screening
Identifieur interne : 000193 ( Main/Exploration ); précédent : 000192; suivant : 000194Identification 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
Affiliations:
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code="subfield">Hong Kong SAR China</wicri:noCountry></affiliation></author><author><name sortKey="Li, Olive Tin Wai" sort="Li, Olive Tin Wai" uniqKey="Li O" first="Olive Tin-Wai" last="Li">Olive Tin-Wai Li</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000121742757</institution-id><institution-id institution-id-type="GRID">grid.194645.b</institution-id><institution>Centre of Influenza Research, School of Public Health, Li Ka Shing Faculty of Medicine,</institution><institution>The University of Hong Kong,</institution></institution-wrap>Shatin, Hong Kong SAR China</nlm:aff><wicri:noCountry code="subfield">Hong Kong SAR China</wicri:noCountry></affiliation></author><author><name sortKey="Tang, Wen Ping" sort="Tang, Wen Ping" uniqKey="Tang W" first="Wen-Ping" last="Tang">Wen-Ping Tang</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 8645 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Chine</country><wicri:regionArea>Shenyang</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Guo Xin" sort="Wang, Guo Xin" uniqKey="Wang G" first="Guo Xin" last="Wang">Guo Xin Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0662 3178</institution-id><institution-id institution-id-type="GRID">grid.12527.33</institution-id><institution>Research Center of Plasmonic and Near-Infrared Science,</institution><institution>Research Institute of Tsinghua University in Shenzhen,</institution></institution-wrap>Shenzhen, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Shenzhen</wicri:regionArea></affiliation></author><author><name sortKey="Ngo, Jacky Chi Ki" sort="Ngo, Jacky Chi Ki" uniqKey="Ngo J" first="Jacky Chi-Ki" last="Ngo">Jacky Chi-Ki Ngo</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1937 0482</institution-id><institution-id institution-id-type="GRID">grid.10784.3a</institution-id><institution>Centre for Protein Science and Crystallography, School of Life Sciences,</institution><institution>The Chinese University of Hong Kong,</institution></institution-wrap>Shatin, Hong Kong SAR China</nlm:aff><wicri:noCountry code="subfield">Hong Kong SAR China</wicri:noCountry></affiliation></author><author><name sortKey="Wan, David Chi Cheong" sort="Wan, David Chi Cheong" uniqKey="Wan D" first="David Chi-Cheong" last="Wan">David Chi-Cheong Wan</name><affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1937 0482</institution-id><institution-id institution-id-type="GRID">grid.10784.3a</institution-id><institution>School of Biomedical Sciences,</institution><institution>The Chinese University of Hong Kong,</institution></institution-wrap>Shatin, Hong Kong SAR China</nlm:aff><wicri:noCountry code="subfield">Hong Kong SAR China</wicri:noCountry></affiliation></author><author><name sortKey="Poon, Leo Lit Man" sort="Poon, Leo Lit Man" uniqKey="Poon L" first="Leo Lit-Man" last="Poon">Leo Lit-Man Poon</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000000121742757</institution-id><institution-id institution-id-type="GRID">grid.194645.b</institution-id><institution>Centre of Influenza Research, School of Public Health, Li Ka Shing Faculty of Medicine,</institution><institution>The University of Hong Kong,</institution></institution-wrap>Shatin, Hong Kong SAR China</nlm:aff><wicri:noCountry code="subfield">Hong Kong SAR China</wicri:noCountry></affiliation></author><author><name sortKey="Shaw, Pang Chui" sort="Shaw, Pang Chui" uniqKey="Shaw P" first="Pang-Chui" last="Shaw">Pang-Chui Shaw</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1937 0482</institution-id><institution-id institution-id-type="GRID">grid.10784.3a</institution-id><institution>Centre for Protein Science and Crystallography, School of Life Sciences,</institution><institution>The Chinese University of Hong Kong,</institution></institution-wrap>Shatin, Hong Kong SAR China</nlm:aff><wicri:noCountry code="subfield">Hong Kong SAR China</wicri:noCountry></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><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><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Chen, H" uniqKey="Chen H">H Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Pflug, A" uniqKey="Pflug A">A Pflug</name></author><author><name sortKey="Guilligay, D" uniqKey="Guilligay D">D Guilligay</name></author><author><name sortKey="Reich, S" uniqKey="Reich S">S Reich</name></author><author><name sortKey="Cusack, S" uniqKey="Cusack S">S Cusack</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reich, S" uniqKey="Reich S">S Reich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stevaert, A" uniqKey="Stevaert A">A Stevaert</name></author><author><name sortKey="Naesens, L" uniqKey="Naesens L">L Naesens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Obayashi, E" uniqKey="Obayashi E">E Obayashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, X" uniqKey="He X">X He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deng, T" uniqKey="Deng T">T Deng</name></author><author><name sortKey="Sharps, J" uniqKey="Sharps J">J Sharps</name></author><author><name sortKey="Fodor, E" uniqKey="Fodor E">E Fodor</name></author><author><name sortKey="Brownlee, Gg" uniqKey="Brownlee G">GG Brownlee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wunderlich, K" uniqKey="Wunderlich K">K Wunderlich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muratore, G" uniqKey="Muratore G">G Muratore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fukuoka, M" uniqKey="Fukuoka M">M Fukuoka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Massari, S" uniqKey="Massari S">S Massari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lepri, S" uniqKey="Lepri S">S Lepri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Massari, S" uniqKey="Massari S">S Massari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Trist, Iml" uniqKey="Trist I">IML Trist</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yuan, S" uniqKey="Yuan S">S Yuan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hara, K" uniqKey="Hara K">K Hara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hu, J" uniqKey="Hu J">J Hu</name></author><author><name sortKey="Liu, X" uniqKey="Liu X">X Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nordstrom, H" uniqKey="Nordstrom H">H Nordström</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perspicace, S" uniqKey="Perspicace S">S Perspicace</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Elinder, M" uniqKey="Elinder M">M Elinder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rich, Rl" uniqKey="Rich R">RL Rich</name></author><author><name sortKey="Myszka, Dg" uniqKey="Myszka D">DG Myszka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lo, Cy" uniqKey="Lo C">CY Lo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perez, Jt" uniqKey="Perez J">JT Perez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lukarska, M" uniqKey="Lukarska M">M Lukarska</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fodor, E" uniqKey="Fodor E">E Fodor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Otw" uniqKey="Li O">OTW Li</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Li, Olive Tin Wai" sort="Li, Olive Tin Wai" uniqKey="Li O" first="Olive Tin-Wai" last="Li">Olive Tin-Wai Li</name><name sortKey="Lo, Chun Yeung" sort="Lo, Chun Yeung" uniqKey="Lo C" first="Chun-Yeung" last="Lo">Chun-Yeung Lo</name><name sortKey="Ngo, Jacky Chi Ki" sort="Ngo, Jacky Chi Ki" uniqKey="Ngo J" first="Jacky Chi-Ki" last="Ngo">Jacky Chi-Ki Ngo</name><name sortKey="Poon, Leo Lit Man" sort="Poon, Leo Lit Man" uniqKey="Poon L" first="Leo Lit-Man" last="Poon">Leo Lit-Man Poon</name><name sortKey="Shaw, Pang Chui" sort="Shaw, Pang Chui" uniqKey="Shaw P" first="Pang-Chui" last="Shaw">Pang-Chui Shaw</name><name sortKey="Wan, David Chi Cheong" sort="Wan, David Chi Cheong" uniqKey="Wan D" first="David Chi-Cheong" last="Wan">David Chi-Cheong Wan</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Tang, Wen Ping" sort="Tang, Wen Ping" uniqKey="Tang W" first="Wen-Ping" last="Tang">Wen-Ping Tang</name></noRegion><name sortKey="Hu, Chun" sort="Hu, Chun" uniqKey="Hu C" first="Chun" last="Hu">Chun Hu</name><name sortKey="Wang, Guo Xin" sort="Wang, Guo Xin" uniqKey="Wang G" first="Guo Xin" last="Wang">Guo Xin Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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