Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (576 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King and Stansfield, A Dictionary of Genetics, 4th ed)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Nucleoside; Nucleoside Analogs; Analogs, Nucleoside; Nucleoside Analog; Analog, Nucleoside.
Where it fits in the MeSH classification
- Broader topics
- Glycosides; Nucleic Acids, Nucleotides, and Nucleosides
- Narrower topics
- Arabinonucleosides; Deoxyribonucleosides; Purine Nucleosides; Pyrimidine Nucleosides; Ribonucleosides; Thionucleosides
Research landscape
PubMed indexes 254,487 records tagged with the MeSH heading “Nucleosides” (counts retrieved 2026-10-31). 30,151 of them (11.8%) were published from 2020 onward, and the busiest period so far is through 1999 with 117,610 records.
Reviews account for 18,750 records (7.4%) and meta-analyses for 1,309. Randomized controlled trials number 9,241 (3.6%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 117,610 |
| 2000-2009 | 52,826 |
| 2010-2019 | 53,900 |
| 2020 onward | 30,151 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 18,750 | 7.4% |
| Meta-analyses | 1,309 | 0.5% |
| Randomized controlled trials | 9,241 | 3.6% |
Method: PubMed query "Nucleosides"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| N4-Acetylcytidine enhances synthetic mRNA translation yield and fidelity | 2026 | Research article Design not recorded in structured metadata | 5 | cc by PMID 42386968 · DOI · PMC13518219 |
| m6A modification suppresses innate anti-tumour immunity in colorectal cancer by limiting alu-derived dsRNA accumulation | 2026 | Research article Design not recorded in structured metadata | 4 | cc by PMID 42135281 · DOI · PMC13377058 |
| Efficacy of the nucleoside analog 4'-Fluorouridine against Nipah virus in the Syrian hamster model | 2026 | Research article Design not recorded in structured metadata | 4 | cc by PMID 41931570 · DOI · PMC13048487 |
N4-Acetylcytidine enhances synthetic mRNA translation yield and fidelity [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Synthetic mRNA therapeutics offer a versatile platform for treating diverse conditions, including cancer and infectious diseases.
- Closing excerpt
- These findings underscore the importance of context in designing therapeutic mRNAs and position the translation elongation rate as a key determinant of the efficacy of modified ribonucleotides.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (199 words)
Synthetic mRNA therapeutics offer a versatile platform for treating diverse conditions, including cancer and infectious diseases. For delivery into cells, these mRNAs are encapsulated in lipid nanoparticles and commonly incorporate modified ribonucleotides to improve stability, enhance translation and mitigate immune recognition1. N1-Methylpseudouridine (m1Ψ) has become the industry standard for synthetic mRNAs owing to its effectiveness in promoting translation and reducing immunogenicity2. However, recent studies have shown that m1Ψ can compromise translational fidelity, leading to errors such as premature termination and ribosomal frameshifting3-5. Here we reveal N4-acetylcytidine (ac4C) as a functionally distinct alternative to m1Ψ. Across cultured cell lines, primary human monocyte-derived dendritic cells and mouse liver, ac4C suppressed inflammatory responses as effectively as m1Ψ while driving higher protein yields. Single-molecule imaging of translation revealed broadly similar ribosome densities per mRNA for ac4C-modified and m1Ψ-modified transcripts. However, translation elongation with m1Ψ-modified mRNA was nearly twofold slower than with ac4C, which resulted in reduced protein output and increased ribosome collisions that further limited protein production through the engagement of quality-control pathways and +1 frameshifting. These findings underscore the importance of context in designing therapeutic mRNAs and position the translation elongation rate as a key determinant of the efficacy of modified ribonucleotides.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42386968 · DOI · PMC13518219
m6A modification suppresses innate anti-tumour immunity in colorectal cancer by limiting alu-derived dsRNA accumulation [2]
Abstract reading summary — source excerpts
- Opening excerpt
- How cancer cells evade immune detection despite expressing immunostimulatory retroelement (RE) transcripts remains unclear.
- Closing excerpt
- Together, our findings identify METTL3 as an RNA-level immune checkpoint and suggest combined METTL3 and DNMT inhibition as a therapeutic strategy in CRC.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (153 words)
How cancer cells evade immune detection despite expressing immunostimulatory retroelement (RE) transcripts remains unclear. In cancer, endogenous REs that escape epigenetic silencing are transcribed and can form double-stranded RNA (dsRNA), which activates innate immune responses through viral mimicry. However, RNA-level mechanisms can limit this effect. Here we show that the m6A RNA methyltransferase METTL3 acts as a key regulator of this suppression in colorectal cancer (CRC). Targeting METTL3 increases the accumulation of dsRNAs derived from both pre-existing and newly transcribed REs, amplifying immunostimulatory signalling and activating cell-intrinsic anti-tumour immunity. CRCs display variable sensitivity to METTL3 inhibition: tumours with high basal dsRNA and RNA methylation respond to METTL3 blockade alone, whereas those with low RNA methylation require combination therapy. Co-treatment with DNA methyltransferase inhibitors (DNMTis) restores immune activation in resistant tumours. Together, our findings identify METTL3 as an RNA-level immune checkpoint and suggest combined METTL3 and DNMT inhibition as a therapeutic strategy in CRC.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42135281 · DOI · PMC13377058
Efficacy of the nucleoside analog 4'-Fluorouridine against Nipah virus in the Syrian hamster model [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Nipah virus (NiV) is a zoonotic paramyxovirus with pandemic potential, for which no licensed vaccines or therapeutics for human use are available.
- Closing excerpt
- This study established proof-of-concept for efficacious oral treatment of lethal NiV infection with a small-molecule nucleoside analog inhibitor in a relevant animal model.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (224 words)
Nipah virus (NiV) is a zoonotic paramyxovirus with pandemic potential, for which no licensed vaccines or therapeutics for human use are available. The nucleoside analog 4'-fluorouridine (4'-FlU, EIDD-2749) has broad activity against RNA viruses including in vitro activity against the Malaysia and Bangladesh clades of NiV (NiV-M and NiV-B, respectively). Here, we report the pharmacokinetic profile of orally administered 4'-FlU in Syrian Golden hamsters and its efficacy against NiV-B. 4'-FlU was orally bioavailable and provided sustained exposure of its bioactive anabolite 4'-FlU 5'-triphosphate (4'-FlU-TP) in the brain. A 7-day treatment course after NiV infection delayed time to death. Extending treatment to 21-28 days reduced viremia, incidence of lung disease, lung lesion severity, inflammation, and mortality. Lesions, viral antigen, or viral RNA could be detected in some survivors, suggesting persistent infections. Sequence analysis of NiV populations showed nonsynonymous single-nucleotide variants (SNVs) in some brain specimens from 4'-FlU-treated animals. Amino acid changes occurred in the nucleocapsid, the polymerase, or the phosphoprotein. It is currently unclear whether they reduce viral susceptibility to treatment or impact virulence but caused a slight increase in 4'-FlU potency compared to the genetic parent virus in vitro. However, none of these SNVs increased viral fitness in human brain astrocytes. This study established proof-of-concept for efficacious oral treatment of lethal NiV infection with a small-molecule nucleoside analog inhibitor in a relevant animal model.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41931570 · DOI · PMC13048487
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Is depression associated with increased oxidative stress? A systematic review and meta-analysis [4]
- Research article Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis [5]
- Research article Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease [6]
- Research article Azathioprine and Risk of Skin Cancer in Organ Transplant Recipients: Systematic Review and Meta-Analysis [7]
- Research article 8-Hydroxy-2-Deoxyguanosine Levels and Cardiovascular Disease: A Systematic Review and Meta-Analysis of the Literature [8]
- Research article Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis [9]
References
- Schiffers S, Nelson BW, Prigge M, Krishna S, Watkins L, Zhu Y, et al.. N4-Acetylcytidine enhances synthetic mRNA translation yield and fidelity. . 2026. PMID 42386968 · DOI · PMC13518219
- Wang Y, Daddi AA, Hosseini A, Kato K, Khalili E, Lindholm HT, et al.. m6A modification suppresses innate anti-tumour immunity in colorectal cancer by limiting alu-derived dsRNA accumulation. . 2026. PMID 42135281 · DOI · PMC13377058
- Escaffre O, Pearson ML, Juelich TL, Smith JK, Zhang L, Lieber CM, et al.. Efficacy of the nucleoside analog 4'-Fluorouridine against Nipah virus in the Syrian hamster model. . 2026. PMID 41931570 · DOI · PMC13048487
- Black CN, Bot M, Scheffer PG, Cuijpers P, Penninx BW. Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology. 2015. PMID 25462890 · DOI
- Galli M, Benenati S, Capodanno D, Franchi F, Rollini F, D'Amario D, et al.. Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis. Lancet. 2021. PMID 33865495 · DOI
- Akbari M, Shah S, Velayos FS, Mahadevan U, Cheifetz AS. Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013. PMID 22434610 · DOI
- Jiyad Z, Olsen CM, Burke MT, Isbel NM, Green AC. Azathioprine and Risk of Skin Cancer in Organ Transplant Recipients: Systematic Review and Meta-Analysis. Am J Transplant. 2016. PMID 27163483 · DOI
- Di Minno A, Turnu L, Porro B, Squellerio I, Cavalca V, Tremoli E, et al.. 8-Hydroxy-2-Deoxyguanosine Levels and Cardiovascular Disease: A Systematic Review and Meta-Analysis of the Literature. Antioxid Redox Signal. 2016. PMID 26650622 · DOI · PMC4827317
- Chiarito M, Sanz-Sánchez J, Cannata F, Cao D, Sturla M, Panico C, et al.. Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis. Lancet. 2020. PMID 32386592 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.