TY - JOUR
T1 - Viruses harness YxxØ motif to interact with host AP2M1 for replication
T2 - A vulnerable broad-spectrum antiviral target
AU - Yuan, Shuofeng
AU - Chu, Hin
AU - Huang, Jingjing
AU - Zhao, Xiaoyu
AU - Ye, Zi Wei
AU - Lai, Pok Man
AU - Wen, Lei
AU - Cai, Jian Piao
AU - Mo, Yufei
AU - Cao, Jianli
AU - Liang, Ronghui
AU - Kwok-Man Poon, Vincent
AU - Sze, Kong Hung
AU - Zhou, Jie
AU - Kai-Wang To, Kelvin
AU - Chen, Zhiwei
AU - Chen, Honglin
AU - Jin, Dong Yan
AU - Fuk-Woo Chan, Jasper
AU - Yuen, Kwok Yung
N1 - Publisher Copyright:
© 2020 The Authors, somerights reserved.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
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U2 - 10.1126/sciadv.aba7910
DO - 10.1126/sciadv.aba7910
M3 - Article
C2 - 32923629
AN - SCOPUS:85090873054
SN - 2375-2548
VL - 6
JO - Science advances
JF - Science advances
IS - 35
M1 - eaba7910
ER -