Evidence map›Paper›PMID 41358724›Full record

ArticleJournal of virology2026

Short-chain fatty acids butyrate and acetate limit Zika virus replication and associated ocular manifestations via the G-protein coupled receptor 43/FFAR2.

Nikhil Deshmukh, Prince Kumar, Lal Krishan Kumar, Vaishnavi Balendiran, Pawan Kumar Singh

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of virology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Nikhil Deshmukh *Department of Ophthalmology, Mason Eye Institute, University of Missouri School of Medicine, Columbia, Missouri, USA.
Prince Kumar *Department of Ophthalmology, Mason Eye Institute, University of Missouri School of Medicine, Columbia, Missouri, USA.
Lal Krishan KumarDepartment of Ophthalmology, Mason Eye Institute, University of Missouri School of Medicine, Columbia, Missouri, USA.
Vaishnavi BalendiranDepartment of Ophthalmology, Mason Eye Institute, University of Missouri School of Medicine, Columbia, Missouri, USA.
Pawan Kumar SinghDepartment of Ophthalmology, Mason Eye Institute, University of Missouri School of Medicine, Columbia, Missouri, USA.ORCID 0000-0001-5517-1120

Funding

Role of Zika virus (ZIKV) infection in glaucoma pathobiologyR01EY032495 · UNIVERSITY OF MISSOURI-COLUMBIA · 2025 to 2025
$346k
NEI NIH HHS R01 EY032495NEI NIH HHS R01EY032495University of Missouri School of Medicine Research Start-up Funds
6 · The paper itself

Abstract

Short-chain fatty acids (SCFAs) are gut microbial metabolites produced by gut microbiota from dietary fiber. SCFAs have shown both pro- and anti-viral roles among different viruses and are known to regulate immune functions during infections. However, their role against the Zika virus (ZIKV), in general, and ocular infection, in particular, has never been investigated. In the present study, we aimed to examine the role of three SCFA derivatives: phenylbutyrate (PBA), sodium butyrate (NaB), and sodium acetate (NaAC), on ZIKV replication and associated ocular complications using primary human trabecular meshwork cells (HTMCs) and an IFNAR1-deficient mouse model of ocular infection. Our findings reveal that PBA and NaAc treatment dramatically suppressed the ZIKV replication in HTMCs. NaB showed a slightly less effect than PBA and NaAc. PBA and NaAc treatment significantly attenuated the ZIKV-induced inflammatory cytokine, interferons, and interferon-stimulated genes response via antagonizing the RIG-I/NFκB/MAPKs/STAT1-3 signaling pathways. We discovered that ZIKV induces the expression of free fatty acid receptor 2 (FFAR2)/GPR43 in HTMCs, which is further potentiated by PBA/NaAc. Pharmacological inhibition of FFAR2 abrogated the protective abilities of PBA/NaAc and significantly increased viral replication. Blocking FFAR2 receptors promoted ZIKV-induced cell death, which was suppressed by PBA and NaAc. Butyrate and acetate also inhibited ZIKV binding and cellular entry and inactivated the virus before internalization. PBA and NaAc treatment in mice attenuated the ZIKV-induced ocular manifestations (intraocular pressure, RPE/retinal atrophy, and TM/anterior segment inflammation), which was abrogated by FFAR2 inhibition by 4-CMTB, a selective pharmacological inhibitor of FFAR2. Collectively, our findings indicate that SCFA treatment is an effective approach to limit ZIKV replication and associated ocular damage and may be worth exploring as a means to treat or prevent ZIKV-induced ocular complications/glaucoma in humans.IMPORTANCEZIKV is known to cause severe ocular manifestations in

Indexed as

AcetatesButyratesButyric AcidFatty Acids, VolatileReceptors, G-Protein-CoupledVirus ReplicationZika VirusZika Virus InfectionAnimalsAntiviral AgentsDisease Models, AnimalHumansMiceMice, Inbred C57BLMice, KnockoutReceptor, Interferon alpha-betaAcetatesAntiviral AgentsButyratesButyric AcidFatty Acids, VolatileFFAR2 protein, humanFfar2 protein, mouseReceptor, Interferon alpha-betaReceptors, G-Protein-CoupledSodium Acetateacetatebutyrateeyeglaucomainflammationintraocular pressureretinal atrophytrabecular meshworkZika virus

Identifiers

PMID41358724
PMCPMC12817915

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.