ArticleScientific reports2016
Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 3 registered trials, which are not on this map. Cited by 112 papers, 6 of them syntheses that pooled it.
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.
The trial behind it
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.
Clinical Trial Evaluating Safety and Efficacy of Ivermectin and Nitazoxanide Combination as Adjuvant Therapy in COVID-19 Newly Diagnosed Egyptian Patients: A Tanta University Hope
Ivermectin to Prevent Hospitalizations in COVID-19: Randomized, Double-blind, Placebo-controlled
The Safety and Efficacy Outcome of Ivermectin Plus Doxycycline in Treatment of RT-PCR Positive Adult Mild Covid-19 Cases: a Randomized Double Blind Placebo Controlled Trial
Who cites it
112 citing papers in PubMed, 6 syntheses or guidelines pooled it, 209 citations in OpenAlex.
- Ivermectin for preventing and treating COVID-19.The Cochrane database of systematic reviews · 2022Pooled it
- Ivermectin under scrutiny: a systematic review and meta-analysis of efficacy and possible sources of controversies in COVID-19 patients.Virology journal · 2022Pooled it
- Ivermectin for preventing and treating COVID-19.The Cochrane database of systematic reviews · 2021Pooled it
- Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen.The Journal of antibiotics · 2020Pooled it
- Chemoprophylaxis against COVID-19 among health-care workers using Ivermectin in low- and middle-income countries: A systematic review and meta-analysis.Indian journal of pharmacologyPooled it
- Ivermectin and mortality in patients with COVID-19: A systematic review, meta-analysis, and meta-regression of randomized controlled trials.Diabetes & metabolic syndromePooled it
- Efficacy of single-dose and double-dose ivermectin early treatment in preventing progression to hospitalization in mild COVID-19: A multi-arm, parallel-group randomized, double-blind, placebo-controlled trial.Respirology (Carlton, Vic.) · 2022Trial
- The effect of ivermectin on the viral load and culture viability in early treatment of nonhospitalized patients with mild COVID-19 - a double-blind, randomized placebo-controlled trial.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2022Trial
- Possible Role of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Recovery of Post-COVID-19 Anosmia.Infection and drug resistance · 2022Trial
- Clinical study evaluating the efficacy of ivermectin in COVID-19 treatment: A randomized controlled study.Journal of medical virology · 2021Trial
- Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial.BMC infectious diseases · 2021Trial
- Trial
- Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19.International journal of nanomedicine · 2021Trial
- Enhanced genome replication activity of pandemic H1N1 influenza A virus through PA mutations.Journal of virology · 2026Article
- Safety and efficacy of different therapeutic regimens in Egyptian adults with moderate COVID-19 infection (EVEREST): a real-world retrospective study.Scientific reports · 2025Article
- A Pilot, Randomised, Placebo-Controlled, Double-Blind Trial of a Single Oral Dose of Ivermectin for Post-Exposure Prophylaxis of SARS-CoV-2.Pharmaceutics · 2025Article
- Decoding non-human mammalian adaptive signatures of 2.3.4.4b H5N1 to assess its human adaptive potential.Microbiology spectrum · 2025Article
- Viral factors underlying the pandemic potential of influenza viruses.Microbiology and molecular biology reviews : MMBR · 2025Review
- H5N1 2.3.4.4b: a review of mammalian adaptations and risk of pandemic emergence.The Journal of general virology · 2025Review
- Heterozygous and generalist MxA super-restrictors overcome breadth-specificity trade-offs in antiviral restriction.Science advances · 2025Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To establish a new lineage in the human population, avian influenza A viruses (AIV) must overcome the intracellular restriction factor MxA. Partial escape from MxA restriction can be achieved when the viral nucleoprotein (NP) acquires the critical human-adaptive amino acid residues 100I/V, 283P, and 313Y. Here, we show that introduction of these three residues into the NP of an avian H5N1 virus renders it genetically unstable, resulting in viruses harboring additional single mutations, including G16D. These substitutions restored genetic stability yet again yielded viruses with varying degrees of attenuation in mammalian and avian cells. Additionally, most of the mutant viruses lost the capacity to escape MxA restriction, with the exception of the G16D virus. We show that MxA escape is linked to attenuation by demonstrating that the three substitutions promoting MxA escape disturbed intracellular trafficking of incoming viral ribonucleoprotein complexes (vRNPs), thereby resulting in impaired nuclear import, and that the additional acquired mutations only partially compensate for this import block. We conclude that for adaptation to the human host, AIV must not only overcome MxA restriction but also an associated block in nuclear vRNP import. This inherent difficulty may partially explain the frequent failure of AIV to become pandemic.
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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.