Evidence map›Paper›PMID 34257311›Full record

ArticleNature communications2021

Reprogrammed CRISPR-Cas13b suppresses SARS-CoV-2 replication and circumvents its mutational escape through mismatch tolerance.

Mohamed Fareh, Wei Zhao, Wenxin Hu, Joshua M L Casan, Amit Kumar, Jori Symons, Jennifer M Zerbato, Danielle Fong, Ilia Voskoboinik, Paul G Ekert and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.4field-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

44 citing papers in PubMed, 66 citations in OpenAlex.

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  11. Ultrasensitive and highly specific detection of theJournal of clinical microbiology · 2025
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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

14 authors at 2 institutions in 1 country.

Mohamed FarehCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia. Mohamed.fareh@petermac.org.ORCID 0000-0001-9551-8213
Wei ZhaoThe Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Wenxin HuCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.ORCID 0000-0002-0330-5200
Joshua M L CasanCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.ORCID 0000-0002-4322-8561
Amit KumarCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.
Jori SymonsThe Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Jennifer M ZerbatoThe Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0001-9888-661X
Danielle FongThe Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0001-9256-9912
Ilia VoskoboinikCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.
Paul G EkertCancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.ORCID 0000-0002-2976-8617
Rajeev RudrarajuThe Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Damian F J PurcellDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Sharon R Lewin *The Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. sharon.lewin@unimelb.edu.au.ORCID 0000-0002-0330-8241
Joseph A Trapani *Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.
The University of Melbourne · AUPeter MacCallum Cancer Centre · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The recent dramatic appearance of variants of concern of SARS-coronavirus-2 (SARS-CoV-2) highlights the need for innovative approaches that simultaneously suppress viral replication and circumvent viral escape from host immunity and antiviral therapeutics. Here, we employ genome-wide computational prediction and single-nucleotide resolution screening to reprogram CRISPR-Cas13b against SARS-CoV-2 genomic and subgenomic RNAs. Reprogrammed Cas13b effectors targeting accessible regions of Spike and Nucleocapsid transcripts achieved >98% silencing efficiency in virus-free models. Further, optimized and multiplexed Cas13b CRISPR RNAs (crRNAs) suppress viral replication in mammalian cells infected with replication-competent SARS-CoV-2, including the recently emerging dominant variant of concern B.1.1.7. The comprehensive mutagenesis of guide-target interaction demonstrated that single-nucleotide mismatches does not impair the capacity of a potent single crRNA to simultaneously suppress ancestral and mutated SARS-CoV-2 strains in infected mammalian cells, including the Spike D614G mutant. The specificity, efficiency and rapid deployment properties of reprogrammed Cas13b described here provide a molecular blueprint for antiviral drug development to suppress and prevent a wide range of SARS-CoV-2 mutants, and is readily adaptable to other emerging pathogenic viruses.

Indexed as

MutationAnimalsAntiviral AgentsChlorocebus aethiopsClustered Regularly Interspaced Short Palindromic RepeatsCOVID-19COVID-19 Drug TreatmentCRISPR-Cas SystemsDrug DevelopmentGenome, ViralHEK293 CellsHumansSARS-CoV-2Spike Glycoprotein, CoronavirusVero CellsVirus ReplicationAntiviral AgentsSpike Glycoprotein, Coronavirus

Identifiers

PMID34257311
PMCPMC8277810
OpenAlexW3181579162

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.