ArticlePLoS pathogens2019
Viral engagement with host receptors blocked by a novel class of tryptophan dendrimers that targets the 5-fold-axis of the enterovirus-A71 capsid.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Endolysosomal two-pore channels regulate a conserved entry pathway for enteroviruses.The Journal of general virology · 2026Article
- The kynurenine pathway in RNA virus infection: immunometabolic control of antiviral defense and viral persistence.Frontiers in immunology · 2026Review
- Antiviral candidates for enterovirus 71: targeting viral proteome and stage-specific lifecycle interventions.Virology journal · 2025Review
- Review
- Advances in anti-EV-A71 drug development research.Journal of advanced research · 2024Review
- Multiplexed multicolor antiviral assay amenable for high-throughput research.Nature communications · 2024Article
- C-2 Thiophenyl Tryptophan Trimers Inhibit Cellular Entry of SARS-CoV-2 through Interaction with the Viral Spike (S) Protein.Journal of medicinal chemistry · 2023Article
- Evaluation of 3D Human Intestinal Organoids as a Platform for EV-A71 Antiviral Drug Discovery.Cells · 2023Article
- Article
- Insertion of an Amphipathic Linker in a Tetrapodal Tryptophan Derivative Leads to a Novel and Highly Potent Entry Inhibitor of Enterovirus A71 Clinical Isolates.International journal of molecular sciences · 2023Article
- 3,4-Dicaffeoylquinic Acid from the Medicinal PlantJournal of virology · 2022Article
- Enterovirus A71 antivirals: Past, present, and future.Acta pharmaceutica Sinica. B · 2022Article
- Functional Insights into Silymarin as an Antiviral Agent against Enterovirus A71 (EV-A71).International journal of molecular sciences · 2021Article
- Double Arylation of the Indole Side Chain of Tri- and Tetrapodal Tryptophan Derivatives Renders Highly Potent HIV-1 and EV-A71 Entry Inhibitors†.Journal of medicinal chemistry · 2021Article
- Multivalent Tryptophan- and Tyrosine-Containing [60]Fullerene Hexa-Adducts as Dual HIV and Enterovirus A71 Entry Inhibitors.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Novel capsid binder and PI4KIIIbeta inhibitors for EV-A71 replication inhibition.Scientific reports · 2021Article
- Antivirals blocking entry of enteroviruses and therapeutic potential.Journal of biomedical science · 2021Review
- Spike glycoproteins: Their significance for corona viruses and receptor binding activities for pathogenesis and viral survival.Microbial pathogenesis · 2021Review
- Rosmarinic acid exhibits broad anti-enterovirus A71 activity by inhibiting the interaction between the five-fold axis of capsid VP1 and cognate sulfated receptors.Emerging microbes & infections · 2020Article
- Rational design of highly potent broad-spectrum enterovirus inhibitors targeting the nonstructural protein 2C.PLoS biology · 2020Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enterovirus A71 (EV-A71) is a non-polio neurotropic enterovirus with pandemic potential. There are no antiviral agents approved to prevent or treat EV-A71 infections. We here report on the molecular mechanism by which a novel class of tryptophan dendrimers inhibits (at low nanomolar to high picomolar concentration) EV-A71 replication in vitro. A lead compound in the series (MADAL385) prevents binding and internalization of the virus but does not, unlike classical capsid binders, stabilize the particle. By means of resistance selection, reverse genetics and cryo-EM, we map the binding region of MADAL385 to the 5-fold vertex of the viral capsid and demonstrate that a single molecule binds to each vertex. By interacting with this region, MADAL385 prevents the interaction of the virus with its cellular receptors PSGL1 and heparan sulfate, thereby blocking the attachment of EV-A71 to the host cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.