ArticleJournal of virology2014
New small molecule entry inhibitors targeting hemagglutinin-mediated influenza a virus fusion.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 86 citations in OpenAlex.
- Article
- Deoxyshikonin Inhibits Influenza A Virus Infection at an Early Stage.International journal of molecular sciences · 2025Article
- Small Molecule Influenza Virus Fusion Inhibitors Targeting Viral Hemagglutinin: Chemical Insights and Antiviral Evaluation.Mini reviews in medicinal chemistry · 2025Review
- An orally active entry inhibitor of influenza A viruses protects mice and synergizes with oseltamivir and baloxavir marboxil.Science advances · 2024Article
- Therapeutic effect of Yinhuapinggan granules mediated through the intestinal flora in mice infected with the H1N1 influenza virus.Frontiers in microbiology · 2024Article
- Antiviral Compounds to Address Influenza Pandemics: An Update from 2016-2022.Current medicinal chemistry · 2024Review
- Potential cross-species transmission of highly pathogenic avian influenza H5 subtype (HPAI H5) viruses to humans calls for the development of H5-specific and universal influenza vaccines.Cell discovery · 2023Review
- Review
- Antiviral Effect of Ginsenosides rk1 against Influenza a Virus Infection by Targeting the Hemagglutinin 1-Mediated Virus Attachment.International journal of molecular sciences · 2023Article
- Therapeutic applications of nanobodies against SARS-CoV-2 and other viral infections: Current update.International journal of biological macromolecules · 2023Review
- Pseudotyped Viruses for Retroviruses.Advances in experimental medicine and biology · 2023Article
- Broad-Spectrum Activity of Small Molecules Acting against Influenza a Virus: Biological and Computational Studies.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Aryl Sulfonamide Inhibits Entry and Replication of Diverse Influenza Viruses via the Hemagglutinin Protein.Journal of medicinal chemistry · 2021Article
- Small Molecule Inhibitors of Influenza Virus Entry.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Potent sialic acid inhibitors that target influenza A virus hemagglutinin.Scientific reports · 2021Article
- Identification of a novel inhibitor targeting influenza A virus group 2 hemagglutinins.Antiviral research · 2021Article
- Non-Toxic Virucidal Macromolecules Show High Efficacy Against Influenza Virus Ex Vivo and In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Temporin G, an amphibian antimicrobial peptide against influenza and parainfluenza respiratory viruses: Insights into biological activity and mechanism of action.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Entry Inhibitors: Efficient Means to Block Viral Infection.The Journal of membrane biology · 2020Review
- Structure of avian influenza hemagglutinin in complex with a small molecule entry inhibitor.Life science alliance · 2020Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
Influenza viruses are a major public health threat worldwide, and options for antiviral therapy are limited by the emergence of drug-resistant virus strains. The influenza virus glycoprotein hemagglutinin (HA) plays critical roles in the early stage of virus infection, including receptor binding and membrane fusion, making it a potential target for the development of anti-influenza drugs. Using pseudotype virus-based high-throughput screens, we have identified several new small molecules capable of inhibiting influenza virus entry. We prioritized two novel inhibitors, MBX2329 and MBX2546, with aminoalkyl phenol ether and sulfonamide scaffolds, respectively, that specifically inhibit HA-mediated viral entry. The two compounds (i) are potent (50% inhibitory concentration [IC50] of 0.3 to 5.9 μM); (ii) are selective (50% cytotoxicity concentration [CC(50)] of >100 μM), with selectivity index (SI) values of >20 to 200 for different influenza virus strains; (iii) inhibit a wide spectrum of influenza A viruses, which includes the 2009 pandemic influenza virus A/H1N1/2009, highly pathogenic avian influenza (HPAI) virus A/H5N1, and oseltamivir-resistant A/H1N1 strains; (iv) exhibit large volumes of synergy with oseltamivir (36 and 331 μM(2) % at 95% confidence); and (v) have chemically tractable structures. Mechanism-of-action studies suggest that both MBX2329 and MBX2546 bind to HA in a nonoverlapping manner. Additional results from HA-mediated hemolysis of chicken red blood cells (cRBCs), competition assays with monoclonal antibody (MAb) C179, and mutational analysis suggest that the compounds bind in the stem region of the HA trimer and inhibit HA-mediated fusion. Therefore, MBX2329 and MBX2546 represent new starting points for chemical optimization and have the potential to provide valuable future therapeutic options and research tools to study the HA-mediated entry process.
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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.