ArticleAntimicrobial agents and chemotherapy2013
Structure-based discovery of the novel antiviral properties of naproxen against the nucleoprotein of influenza A virus.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 137 citations in OpenAlex.
- In Vitro Evaluation of Acetaminophen as a Repurposed Anti-Influenza Virus Agent.Biotechnology and applied biochemistry · 2026Article
- A Structural View of Influenza Virus Ribonucleoprotein Complex and Its Functions.Microorganisms · 2026Review
- Drug repositioning as a promising approach for the eradication of emerging and re-emerging viral agents.Molecular diversity · 2025Review
- Computational Discovery of Potent Nucleoprotein Inhibitors for Influenza A Virus: Validation Through QM/MM Analysis and Experimental Binding Assays.Molecules (Basel, Switzerland) · 2025Article
- Progress of Influenza Viruses and Inhibitors.Current medicinal chemistry · 2025Review
- Suppression of Interferon Response and Antiviral Strategies of Bunyaviruses.Tropical medicine and infectious disease · 2024Review
- Long Neuro-COVID-19: Current Mechanistic Views and Therapeutic Perspectives.Biomolecules · 2024Review
- Evaluating NSAIDs in SARS-CoV-2: Immunomodulatory mechanisms and future therapeutic strategies.Heliyon · 2024Review
- Integrating Artificial Intelligence for Drug Discovery in the Context of Revolutionizing Drug Delivery.Life (Basel, Switzerland) · 2024Review
- Emerging drug design strategies in anti-influenza drug discovery.Acta pharmaceutica Sinica. B · 2023Review
- Novel Molecular Consortia of Cannabidiol with Nonsteroidal Anti-Inflammatory Drugs Inhibit Emerging Coronaviruses' Entry.Pathogens (Basel, Switzerland) · 2023Article
- Antiviral options and therapeutics against influenza: history, latest developments and future prospects.Frontiers in cellular and infection microbiology · 2023Review
- MicroRNA-205-5p: A potential therapeutic target for influenza A.Journal of cellular and molecular medicine · 2022Article
- Neuropeptides, New Ligands of SARS-CoV-2 Nucleoprotein, a Potential Link between Replication, Inflammation and Neurotransmission.Molecules (Basel, Switzerland) · 2022Article
- Synthesis, crystal structure, and a molecular modeling approach to identify effective antiviral hydrazide derivative against the main protease of SARS-CoV-2.Journal of molecular structure · 2022Article
- Contemporary medicinal chemistry strategies for the discovery and optimization of influenza inhibitors targeting vRNP constituent proteins.Acta pharmaceutica Sinica. B · 2022Review
- NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments.International journal of molecular sciences · 2022Review
- Efficacy and safety profile of corticosteroids and non-steroidal anti-inflammatory drugs in COVID-19 management: A narrative review.Frontiers in pharmacology · 2022Review
- Structure-Property Relationship for Different Mesoporous Silica Nanoparticles and its Drug Delivery Applications: A Review.Frontiers in chemistry · 2022Review
- Repurposing existing drugs: identification of SARS-CoV-2 3C-like protease inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2021Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nucleoprotein (NP) binds the viral RNA genome and associates with the polymerase in a ribonucleoprotein complex (RNP) required for transcription and replication of influenza A virus. NP has no cellular counterpart, and the NP sequence is highly conserved, which led to considering NP a hot target in the search for antivirals. We report here that monomeric nucleoprotein can be inhibited by a small molecule binding in its RNA binding groove, resulting in a novel antiviral against influenza A virus. We identified naproxen, an anti-inflammatory drug that targeted the nucleoprotein to inhibit NP-RNA association required for NP function, by virtual screening. Further docking and molecular dynamics (MD) simulations identified in the RNA groove two NP-naproxen complexes of similar levels of interaction energy. The predicted naproxen binding sites were tested using the Y148A, R152A, R355A, and R361A proteins carrying single-point mutations. Surface plasmon resonance, fluorescence, and other in vitro experiments supported the notion that naproxen binds at a site identified by MD simulations and showed that naproxen competed with RNA binding to wild-type (WT) NP and protected active monomers of the nucleoprotein against proteolytic cleavage. Naproxen protected Madin-Darby canine kidney (MDCK) cells against viral challenges with the H1N1 and H3N2 viral strains and was much more effective than other cyclooxygenase inhibitors in decreasing viral titers of MDCK cells. In a mouse model of intranasal infection, naproxen treatment decreased the viral titers in mice lungs. In conclusion, naproxen is a promising lead compound for novel antivirals against influenza A virus that targets the nucleoprotein in its RNA binding groove.
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