Viruses harness YxxO motif to interact with host AP2M1 for replication: A vulnerable broad-spectrum antiviral target.
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 YxxO-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. YxxO 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.
Mesh Terms:
A549 Cells, Adaptor Proteins, Vesicular Transport, Animals, Antiviral Agents, Betacoronavirus, Binding Sites, COVID-19, Cell Line, Tumor, Chlorocebus aethiops, Cinnamates, Coronavirus Infections, Dogs, HEK293 Cells, HIV Infections, HIV-1, Host-Pathogen Interactions, Humans, Influenza A virus, Influenza, Human, Madin Darby Canine Kidney Cells, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Middle East Respiratory Syndrome Coronavirus, Pandemics, Pneumonia, Viral, Protein Binding, Protein Transport, RNA, Viral, Receptor, Interferon alpha-beta, SARS-CoV-2, Transforming Growth Factor beta1, Vero Cells, Virus Replication, Zika Virus, Zika Virus Infection, ortho-Aminobenzoates
A549 Cells, Adaptor Proteins, Vesicular Transport, Animals, Antiviral Agents, Betacoronavirus, Binding Sites, COVID-19, Cell Line, Tumor, Chlorocebus aethiops, Cinnamates, Coronavirus Infections, Dogs, HEK293 Cells, HIV Infections, HIV-1, Host-Pathogen Interactions, Humans, Influenza A virus, Influenza, Human, Madin Darby Canine Kidney Cells, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Middle East Respiratory Syndrome Coronavirus, Pandemics, Pneumonia, Viral, Protein Binding, Protein Transport, RNA, Viral, Receptor, Interferon alpha-beta, SARS-CoV-2, Transforming Growth Factor beta1, Vero Cells, Virus Replication, Zika Virus, Zika Virus Infection, ortho-Aminobenzoates
Sci Adv
Date: Aug. 01, 2020
PubMed ID: 32923629
View in: Pubmed Google Scholar
Download Curated Data For This Publication
241564
Switch View:
- Interactions 1
- Chemical Interactions 1