ArticlePLoS pathogens2020
Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Target-Based Antiviral Drug Development Against Human Respiratory Viruses.Pathogens (Basel, Switzerland) · 2026Review
- Adamantane-based inhibitors of the influenza A M2 proton channel: structure-based design, biological evaluation, and synthetic approaches.RSC medicinal chemistry · 2026Review
- A novel C-3-substituted oleanolic acid benzyl amide derivative exhibits therapeutic potential against influenza A by targeting PA-PB1 interactions and modulating host macrophage inflammation.Acta pharmaceutica Sinica. B · 2025Article
- Molecular biophysics and inhibition mechanism of influenza virus A M2 viroporin by adamantane-based drugs - Challenges in designing antiviral agents.Journal of structural biology: X · 2025Article
- The 6-kilodalton peptide 1 of the familyFrontiers in microbiology · 2025Review
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- Screening for anti-influenza virus compounds from traditional Mongolian medicine by GFP-based reporter virus.Frontiers in cellular and infection microbiology · 2024Article
- Biocompatible Iron Oxide Nanoparticles Display Antiviral Activity Against Two Different Respiratory Viruses in Mice.International journal of nanomedicine · 2024Article
- The convergent evolution of influenza A virus: Implications, therapeutic strategies and what we need to know.Current research in microbial sciences · 2023Article
- Functions of Viroporins in the Viral Life Cycle and Their Regulation of Host Cell Responses.Frontiers in immunology · 2022Review
- Microsecond molecular dynamics simulations revealed the inhibitory potency of amiloride analogs against SARS-CoV-2 E viroporin.Genomics & informatics · 2021Article
- Development and Effects of Influenza Antiviral Drugs.Molecules (Basel, Switzerland) · 2021Review
- Highlighting membrane protein structure and function: A celebration of the Protein Data Bank.The Journal of biological chemistryReview
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 1 country.
Funding
Abstract
Pandemic influenza A virus (IAV) remains a significant threat to global health. Preparedness relies primarily upon a single class of neuraminidase (NA) targeted antivirals, against which resistance is steadily growing. The M2 proton channel is an alternative clinically proven antiviral target, yet a near-ubiquitous S31N polymorphism in M2 evokes resistance to licensed adamantane drugs. Hence, inhibitors capable of targeting N31 containing M2 (M2-N31) are highly desirable. Rational in silico design and in vitro screens delineated compounds favouring either lumenal or peripheral M2 binding, yielding effective M2-N31 inhibitors in both cases. Hits included adamantanes as well as novel compounds, with some showing low micromolar potency versus pandemic "swine" H1N1 influenza (Eng195) in culture. Interestingly, a published adamantane-based M2-N31 inhibitor rapidly selected a resistant V27A polymorphism (M2-A27/N31), whereas this was not the case for non-adamantane compounds. Nevertheless, combinations of adamantanes and novel compounds achieved synergistic antiviral effects, and the latter synergised with the neuraminidase inhibitor (NAi), Zanamivir. Thus, site-directed drug combinations show potential to rejuvenate M2 as an antiviral target whilst reducing the risk of drug resistance.
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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.