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Article: Viruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target

TitleViruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target
Authors
KeywordsAnthranilic acid
Broad spectrum
Endoplasmic reticulum
Human immunodeficiency virus
Influenza A virus
Issue Date2020
PublisherAmerican 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?
AbstractTargeting 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 Identifierhttp://hdl.handle.net/10722/290055
ISSN
2019 Impact Factor: 13.116
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorYuan, S-
dc.contributor.authorChu, H-
dc.contributor.authorHuang, J-
dc.contributor.authorZhao, X-
dc.contributor.authorYe, ZW-
dc.contributor.authorLai, PM-
dc.contributor.authorWen, L-
dc.contributor.authorCai, JP-
dc.contributor.authorMo, Y-
dc.contributor.authorCao, J-
dc.contributor.authorLiang, R-
dc.contributor.authorPoon, VKM-
dc.contributor.authorSze, KH-
dc.contributor.authorZhou, J-
dc.contributor.authorTo, KKW-
dc.contributor.authorChen, Z-
dc.contributor.authorChen, H-
dc.contributor.authorJin, D-
dc.contributor.authorChan, JFW-
dc.contributor.authorYuen, KY-
dc.date.accessioned2020-10-22T08:21:27Z-
dc.date.available2020-10-22T08:21:27Z-
dc.date.issued2020-
dc.identifier.citationScience Advances, 2020, v. 6 n. 35, p. article no. eaba7910-
dc.identifier.issn2375-2548-
dc.identifier.urihttp://hdl.handle.net/10722/290055-
dc.description.abstractTargeting 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.languageeng-
dc.publisherAmerican Association for the Advancement of Science: Science Advances. The Journal's web site is located at http://www.scienceadvances.org/-
dc.relation.ispartofScience Advances-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAnthranilic acid-
dc.subjectBroad spectrum-
dc.subjectEndoplasmic reticulum-
dc.subjectHuman immunodeficiency virus-
dc.subjectInfluenza A virus-
dc.titleViruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target-
dc.typeArticle-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailYe, ZW: zwye@hku.hk-
dc.identifier.emailSze, KH: khsze@hku.hk-
dc.identifier.emailZhou, J: jiezhou@hku.hk-
dc.identifier.emailTo, KKW: kelvinto@hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.emailChen, H: hlchen@hku.hk-
dc.identifier.emailJin, D: dyjin@hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityYuan, S=rp02640-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authoritySze, KH=rp00785-
dc.identifier.authorityZhou, J=rp01412-
dc.identifier.authorityTo, KKW=rp01384-
dc.identifier.authorityChen, Z=rp00243-
dc.identifier.authorityChen, H=rp00383-
dc.identifier.authorityJin, D=rp00452-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1126/sciadv.aba7910-
dc.identifier.pmid32923629-
dc.identifier.pmcidPMC7455044-
dc.identifier.scopuseid_2-s2.0-85090873054-
dc.identifier.hkuros316415-
dc.identifier.volume6-
dc.identifier.issue35-
dc.identifier.spagearticle no. eaba7910-
dc.identifier.epagearticle no. eaba7910-
dc.publisher.placeUnited States-

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