2. Academic Validation
  3. Viruses harness YxxØ motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target

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

  • Sci Adv. 2020 Aug 28;6(35):eaba7910. doi: 10.1126/sciadv.aba7910.
Shuofeng Yuan 1 2 3 4,  Hin Chu 1 2 3 4,  Jingjing Huang 2,  Xiaoyu Zhao 2,  Zi-Wei Ye 2,  Pok-Man Lai 2,  Lei Wen 2,  Jian-Piao Cai 2,  Yufei Mo 5,  Jianli Cao 2,  Ronghui Liang 2,  Vincent Kwok-Man Poon 2,  Kong-Hung Sze 1 2 3,  Jie Zhou 1 2 3 4,  Kelvin Kai-Wang To 1 2 3 4 5,  Zhiwei Chen 1 2 3 6,  Honglin Chen 1 2 3 4,  Dong-Yan Jin 7,  Jasper Fuk-Woo Chan 1 2 3 4 5 8,  Kwok-Yung Yuen 1 2 3 4 5 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • 2 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • 3 Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • 4 Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
  • 5 Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, China.
  • 6 AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
  • 7 School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
  • 8 Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, Hainan, China.
PMID: 32923629 DOI: 10.1126/sciadv.aba7910
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.

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