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Article: Viruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target
Title | Viruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target |
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Authors | |
Keywords | Anthranilic acid Broad spectrum Endoplasmic reticulum Human immunodeficiency virus Influenza A virus |
Issue Date | 2020 |
Publisher | American Association for the Advancement of Science: Science Advances. The Journal's web site is located at http://www.scienceadvances.org/ |
Citation | Science Advances, 2020, v. 6 n. 35, p. article no. eaba7910 How to Cite? |
Abstract | Targeting a universal host protein exploited by most viruses would be a game-changing strategy that offers broad-spectrum solution and rapid pandemic control including the current COVID-19. Here, we found a common YxxØ-motif of multiple viruses that exploits host AP2M1 for intracellular trafficking. A library chemical, N-(p-amylcinnamoyl)anthranilic acid (ACA), was identified to interrupt AP2M1-virus interaction and exhibit potent antiviral efficacy against a number of viruses in vitro and in vivo, including the influenza A viruses (IAVs), Zika virus (ZIKV), human immunodeficiency virus, and coronaviruses including MERS-CoV and SARS-CoV-2. YxxØ mutation, AP2M1 depletion, or disruption by ACA causes incorrect localization of viral proteins, which is exemplified by the failure of nuclear import of IAV nucleoprotein and diminished endoplasmic reticulum localization of ZIKV-NS3 and enterovirus-A71-2C proteins, thereby suppressing viral replication. Our study reveals an evolutionarily conserved mechanism of protein-protein interaction between host and virus that can serve as a broad-spectrum antiviral target. |
Persistent Identifier | http://hdl.handle.net/10722/290055 |
ISSN | 2023 Impact Factor: 11.7 2023 SCImago Journal Rankings: 4.483 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Yuan, S | - |
dc.contributor.author | Chu, H | - |
dc.contributor.author | Huang, J | - |
dc.contributor.author | Zhao, X | - |
dc.contributor.author | Ye, ZW | - |
dc.contributor.author | Lai, PM | - |
dc.contributor.author | Wen, L | - |
dc.contributor.author | Cai, JP | - |
dc.contributor.author | Mo, Y | - |
dc.contributor.author | Cao, J | - |
dc.contributor.author | Liang, R | - |
dc.contributor.author | Poon, VKM | - |
dc.contributor.author | Sze, KH | - |
dc.contributor.author | Zhou, J | - |
dc.contributor.author | To, KKW | - |
dc.contributor.author | Chen, Z | - |
dc.contributor.author | Chen, H | - |
dc.contributor.author | Jin, D | - |
dc.contributor.author | Chan, JFW | - |
dc.contributor.author | Yuen, KY | - |
dc.date.accessioned | 2020-10-22T08:21:27Z | - |
dc.date.available | 2020-10-22T08:21:27Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Science Advances, 2020, v. 6 n. 35, p. article no. eaba7910 | - |
dc.identifier.issn | 2375-2548 | - |
dc.identifier.uri | http://hdl.handle.net/10722/290055 | - |
dc.description.abstract | Targeting a universal host protein exploited by most viruses would be a game-changing strategy that offers broad-spectrum solution and rapid pandemic control including the current COVID-19. Here, we found a common YxxØ-motif of multiple viruses that exploits host AP2M1 for intracellular trafficking. A library chemical, N-(p-amylcinnamoyl)anthranilic acid (ACA), was identified to interrupt AP2M1-virus interaction and exhibit potent antiviral efficacy against a number of viruses in vitro and in vivo, including the influenza A viruses (IAVs), Zika virus (ZIKV), human immunodeficiency virus, and coronaviruses including MERS-CoV and SARS-CoV-2. YxxØ mutation, AP2M1 depletion, or disruption by ACA causes incorrect localization of viral proteins, which is exemplified by the failure of nuclear import of IAV nucleoprotein and diminished endoplasmic reticulum localization of ZIKV-NS3 and enterovirus-A71-2C proteins, thereby suppressing viral replication. Our study reveals an evolutionarily conserved mechanism of protein-protein interaction between host and virus that can serve as a broad-spectrum antiviral target. | - |
dc.language | eng | - |
dc.publisher | American Association for the Advancement of Science: Science Advances. The Journal's web site is located at http://www.scienceadvances.org/ | - |
dc.relation.ispartof | Science Advances | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Anthranilic acid | - |
dc.subject | Broad spectrum | - |
dc.subject | Endoplasmic reticulum | - |
dc.subject | Human immunodeficiency virus | - |
dc.subject | Influenza A virus | - |
dc.title | Viruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target | - |
dc.type | Article | - |
dc.identifier.email | Yuan, S: yuansf@hku.hk | - |
dc.identifier.email | Chu, H: hinchu@hku.hk | - |
dc.identifier.email | Ye, ZW: zwye@hku.hk | - |
dc.identifier.email | Sze, KH: khsze@hku.hk | - |
dc.identifier.email | Zhou, J: jiezhou@hku.hk | - |
dc.identifier.email | To, KKW: kelvinto@hku.hk | - |
dc.identifier.email | Chen, Z: zchenai@hku.hk | - |
dc.identifier.email | Chen, H: hlchen@hku.hk | - |
dc.identifier.email | Jin, D: dyjin@hku.hk | - |
dc.identifier.email | Chan, JFW: jfwchan@hku.hk | - |
dc.identifier.email | Yuen, KY: kyyuen@hkucc.hku.hk | - |
dc.identifier.authority | Yuan, S=rp02640 | - |
dc.identifier.authority | Chu, H=rp02125 | - |
dc.identifier.authority | Sze, KH=rp00785 | - |
dc.identifier.authority | Zhou, J=rp01412 | - |
dc.identifier.authority | To, KKW=rp01384 | - |
dc.identifier.authority | Chen, Z=rp00243 | - |
dc.identifier.authority | Chen, H=rp00383 | - |
dc.identifier.authority | Jin, D=rp00452 | - |
dc.identifier.authority | Chan, JFW=rp01736 | - |
dc.identifier.authority | Yuen, KY=rp00366 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1126/sciadv.aba7910 | - |
dc.identifier.pmid | 32923629 | - |
dc.identifier.pmcid | PMC7455044 | - |
dc.identifier.scopus | eid_2-s2.0-85090873054 | - |
dc.identifier.hkuros | 316415 | - |
dc.identifier.volume | 6 | - |
dc.identifier.issue | 35 | - |
dc.identifier.spage | article no. eaba7910 | - |
dc.identifier.epage | article no. eaba7910 | - |
dc.identifier.isi | WOS:000580595700010 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 2375-2548 | - |