Evidence map›Paper›PMID 41373822›Full record

ArticleInternational journal of molecular sciences2025

Respiratory Delivery of Highly Conserved Antiviral siRNAs Suppress SARS-CoV-2 Infection.

Yuan Zhang, Matt D Johansen, Scott Ledger, Stuart Turville, Pall Thordarson, Philip M Hansbro, Anthony D Kelleher, Chantelle L Ahlenstiel

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Yuan ZhangKirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0000-0003-3270-1082
Matt D JohansenCentre for Inflammation, School of Life Sciences, Faculty of Science, Centenary Institute and University of Technology Sydney, Sydney, NSW 2050, Australia.ORCID 0000-0001-5553-5270
Scott LedgerKirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Stuart TurvilleKirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.
Pall ThordarsonRNA Institute, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0000-0002-1200-8814
Philip M HansbroCentre for Inflammation, School of Life Sciences, Faculty of Science, Centenary Institute and University of Technology Sydney, Sydney, NSW 2050, Australia.ORCID 0000-0002-4741-3035
Anthony D KelleherKirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0000-0002-0009-3337
Chantelle L AhlenstielKirby Institute, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0000-0002-4238-7237

Funding

Australian Government MRFF2017698
6 · The paper itself

Abstract

COVID-19 has resulted in over 777 million confirmed cases and more than 7 million deaths globally. While vaccination offers protection for individuals with a functional immune system, immunocompromised populations will not generate sufficient responses, highlighting the critical need for new antiviral treatments. Here we evaluated four highly conserved anti-COVID siRNAs targeting the ORF1a-Nsp1, Membrane, and Nucleocapsid regions by identifying their antiviral efficacy in vitro and investigated the direct delivery of naked siRNAs to the respiratory tract of mice via intranasal instillation to provide proof-of-concept evidence of their in vivo antiviral activity. Dose-response analysis of siRNAs revealed a range of IC50 0.02 nM to 0.9 nM. Intranasal administration of naked anti-COVID siRNA-18 in a K18-hACE2 transgenic SARS-CoV-2 mouse model was capable of reducing viral mRNA levels and disease severity. While anti-COVID siRNA-30 induced modest interferon-stimulated gene expression in vitro and immune cell infiltration in vivo, these effects were markedly reduced by 2'-O-methyl-AS456 chemical modification, which preserved antiviral efficacy against SARS-CoV-2 while minimizing off-target immune activation. These results demonstrate the feasibility of direct respiratory siRNA administration for in vivo viral suppression and highlight the benefit of using conserved target sequences and chemical modification to enhance therapeutic safety and efficacy.

Indexed as

Antiviral AgentsCOVID-19RNA, Small InterferingSARS-CoV-2Administration, IntranasalAnimalsDisease Models, AnimalFemaleHumansMiceMice, TransgenicAntiviral AgentsRNA, Small Interferingchemical modificationimmunomodulationinnate immune activationrespiratory deliveryRNA interferenceSARS-CoV-2siRNA

Identifiers

PMID41373822
PMCPMC12692593

What OpenQuestion 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 OpenQuestion graph.