Evidence map›Paper›PMID 34928377›Full record

ArticleNucleic acids research2022

Targeting genomic SARS-CoV-2 RNA with siRNAs allows efficient inhibition of viral replication and spread.

Shubhankar Ambike, Cho-Chin Cheng, Martin Feuerherd, Stoyan Velkov, Domizia Baldassi, Suliman Qadir Afridi, Diana Porras-Gonzalez, Xin Wei, Philipp Hagen, Nikolaus Kneidinger and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.6field-weighted citation impact, top 4% of its field
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

38 citing papers in PubMed, 67 citations in OpenAlex.

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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

17 authors at 5 institutions in 2 countries.

Shubhankar AmbikeInstitute of Virology, School of Medicine, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 Munich, Germany.
Cho-Chin ChengInstitute of Virology, School of Medicine, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 Munich, Germany.
Martin FeuerherdInstitute of Virology, School of Medicine, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 Munich, Germany.
Stoyan VelkovInstitute of Virology, School of Medicine, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 Munich, Germany.
Domizia BaldassiDepartment of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, Butenandtstraße 5, 81377 Munich, Germany.
Suliman Qadir AfridiInstitute of Virology, School of Medicine, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 Munich, Germany.
Diana Porras-GonzalezInstitute of Lung Biology and Disease (ILBD) and Comprehensive Pneumology Center (CPC) with the CPC-M bioArchive, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
Xin WeiInstitute of Lung Biology and Disease (ILBD) and Comprehensive Pneumology Center (CPC) with the CPC-M bioArchive, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
Philipp HagenInstitute of Virology, School of Medicine, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 Munich, Germany.
Nikolaus KneidingerDepartment of Medicine V, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
Mircea Gabriel StoleriuCenter for Thoracic Surgery Munich, Ludwig-Maximilians-University of Munich (LMU) and Asklepios Pulmonary Hospital; Marchioninistraße 15, 81377 Munich and Robert-Koch-Allee 2, 82131 Gauting, Germany.
Vincent GrassInstitute of Virology, School of Medicine, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 Munich, Germany.
Gerald BurgstallerInstitute of Lung Biology and Disease (ILBD) and Comprehensive Pneumology Center (CPC) with the CPC-M bioArchive, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
Andreas PichlmairInstitute of Virology, School of Medicine, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 Munich, Germany.
Olivia M MerkelDepartment of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, Butenandtstraße 5, 81377 Munich, Germany.
Chunkyu KoInstitute of Virology, School of Medicine, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 Munich, Germany.
Thomas MichlerInstitute of Virology, School of Medicine, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 Munich, Germany.
Helmholtz Zentrum München · DETechnical University of Munich · DELudwig-Maximilians-Universität München · DEGerman Center for Infection Research · DEGerman Center for Lung Research · DE

Funding

Bavarian State GovernmentElse Kroener-Research CollegeERC ERC-StG 637830German Academic Exchange ServiceGerman Federal Ministry of Education and ResearchGerman Research Foundation PI1084/5Volkswagen Foundation
6 · The paper itself

Abstract

A promising approach to tackle the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) could be small interfering (si)RNAs. So far it is unclear, which viral replication steps can be efficiently inhibited with siRNAs. Here, we report that siRNAs can target genomic RNA (gRNA) of SARS-CoV-2 after cell entry, and thereby terminate replication before start of transcription and prevent virus-induced cell death. Coronaviruses replicate via negative sense RNA intermediates using a unique discontinuous transcription process. As a result, each viral RNA contains identical sequences at the 5' and 3' end. Surprisingly, siRNAs were not active against intermediate negative sense transcripts. Targeting common sequences shared by all viral transcripts allowed simultaneous suppression of gRNA and subgenomic (sg)RNAs by a single siRNA. The most effective suppression of viral replication and spread, however, was achieved by siRNAs that targeted open reading frame 1 (ORF1) which only exists in gRNA. In contrast, siRNAs that targeted the common regions of transcripts were outcompeted by the highly abundant sgRNAs leading to an impaired antiviral efficacy. Verifying the translational relevance of these findings, we show that a chemically modified siRNA that targets a highly conserved region of ORF1, inhibited SARS-CoV-2 replication ex vivo in explants of the human lung. Our work encourages the development of siRNA-based therapies for COVID-19 and suggests that early therapy start, or prophylactic application, together with specifically targeting gRNA, might be key for high antiviral efficacy.

Indexed as

RNA, Small InterferingRNA, ViralVirus Replication3' Untranslated RegionsAnimalsAntiviral AgentsCell SurvivalCOVID-19COVID-19 Drug TreatmentDatabases, GeneticHEK293 CellsHumansLungNucleic Acid ConformationOligonucleotidesOpen Reading Frames3' Untranslated RegionsAntiviral AgentsOligonucleotidesRNA, Small InterferingRNA, Viral

Identifiers

PMID34928377
PMCPMC8754636
OpenAlexW4200317975

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.