ArticleJournal of biomolecular structure & dynamics2015
Structure-based design of novel naproxen derivatives targeting monomeric nucleoprotein of Influenza A virus.
Article in Journal of biomolecular structure & dynamics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- Progress of Influenza Viruses and Inhibitors.Current medicinal chemistry · 2025Review
- Novel Molecular Consortia of Cannabidiol with Nonsteroidal Anti-Inflammatory Drugs Inhibit Emerging Coronaviruses' Entry.Pathogens (Basel, Switzerland) · 2023Article
- Efficacy and safety profile of corticosteroids and non-steroidal anti-inflammatory drugs in COVID-19 management: A narrative review.Frontiers in pharmacology · 2022Review
- Targeting the N-Terminus Domain of the Coronavirus Nucleocapsid Protein Induces Abnormal Oligomerization via Allosteric Modulation.Frontiers in molecular biosciences · 2022Article
- Drug-based therapeutic strategies for COVID-19-infected patients and their challenges.Future microbiology · 2021Review
- Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus.Molecules (Basel, Switzerland) · 2021Article
- Anti-Influenza Drug Discovery and Development: Targeting the Virus and Its Host by All Possible Means.Advances in experimental medicine and biology · 2021Article
- Article
- Coronavirus Disease 2019 (COVID-19) and Transplantation: Pharmacotherapeutic Management of Immunosuppression Regimen.Therapeutics and clinical risk management · 2020Review
- Anti-Influenza Treatment: Drugs Currently Used and Under Development.Archivos de bronconeumologia · 2017Review
- Influenza A Virus Nucleoprotein: A Highly Conserved Multi-Functional Viral Protein as a Hot Antiviral Drug Target.Current topics in medicinal chemistry · 2017Review
- The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design.Medicinal research reviews · 2016Review
- Meeting report: 4th ISIRV antiviral group conference: Novel antiviral therapies for influenza and other respiratory viruses.Antiviral research · 2016Article
- Recent insights into the development of therapeutics against coronavirus diseases by targeting N protein.Drug discovery today · 2016Review
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nucleoprotein (NP) binds the viral RNA genome as oligomers assembled with the polymerase in a ribonucleoprotein complex required for transcription and replication of influenza A virus. Novel antiviral candidates targeting the nucleoprotein either induced higher order oligomers or reduced NP oligomerization by targeting the oligomerization loop and blocking its insertion into adjacent nucleoprotein subunit. In this study, we used a different structure-based approach to stabilize monomers of the nucleoprotein by drugs binding in its RNA-binding groove. We recently identified naproxen as a drug competing with RNA binding to NP with antiinflammatory and antiviral effects against influenza A virus. Here, we designed novel derivatives of naproxen by fragment extension for improved binding to NP. Molecular dynamics simulations suggested that among these derivatives, naproxen A and C0 were most promising. Their chemical synthesis is described. Both derivatives markedly stabilized NP monomer against thermal denaturation. Naproxen C0 bound tighter to NP than naproxen at a binding site predicted by MD simulations and shown by competition experiments using wt NP or single-point mutants as determined by surface plasmon resonance. MD simulations suggested that impeded oligomerization and stabilization of monomeric NP is likely to be achieved by drugs binding in the RNA grove and inducing close to their binding site conformational changes of key residues hosting the oligomerization loop as observed for the naproxen derivatives. Naproxen C0 is a potential antiviral candidate blocking influenza nucleoprotein function.
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