Evidence map›Paper›PMID 32943628›Full record

ArticleNature communications2020

Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis.

Ashleigh Shannon, Barbara Selisko, Nhung-Thi-Tuyet Le, Johanna Huchting, Franck Touret, Géraldine Piorkowski, Véronique Fattorini, François Ferron, Etienne Decroly, Chris Meier and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
186citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% 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

186 citing papers in PubMed, 1 synthesis or guideline pooled it, 298 citations in OpenAlex.

  1. The efficacy and adverse effects of favipiravir on patients with COVID-19: A systematic review and meta-analysis of published clinical trials and observational studies.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2022
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  13. Mutation rate variability in viral populations: Implications for lethal mutagenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
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126 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 3 countries.

Ashleigh ShannonArchitecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.ORCID http://orcid.org/0000-0003-4290-8247
Barbara SeliskoArchitecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.ORCID http://orcid.org/0000-0001-7135-4357
Nhung-Thi-Tuyet LeArchitecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.
Johanna HuchtingFaculty of Sciences, Department of Chemistry, Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, D-20146, Hamburg, Germany.ORCID http://orcid.org/0000-0001-6368-3273
Franck TouretUnité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France.ORCID http://orcid.org/0000-0002-4734-2249
Géraldine PiorkowskiUnité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France.
Véronique FattoriniArchitecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.ORCID http://orcid.org/0000-0001-6420-7949
François FerronArchitecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.ORCID http://orcid.org/0000-0002-8351-4992
Etienne DecrolyArchitecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France.ORCID http://orcid.org/0000-0002-6046-024X
Chris MeierFaculty of Sciences, Department of Chemistry, Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, D-20146, Hamburg, Germany.
Bruno CoutardUnité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France.
Olve PeersenDepartment of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, CO, 80523-1870, USA. Olve.Peersen@colostate.edu.ORCID http://orcid.org/0000-0001-6208-2660
Bruno CanardArchitecture et Fonction des Macromolécules Biologiques, CNRS and Aix-Marseille Université, UMR 7257, 13009, Marseille, France. bruno.canard@afmb.univ-mrs.fr.
Centre National de la Recherche Scientifique · FRInserm · FRUniversität Hamburg · DEColorado State University · US

Funding

Assembly of Picornaviral Replication ComplexesR01AI059130 · NIAID · COLORADO STATE UNIVERSITY-FORT COLLINS · PI PEERSEN, OLVE BREIEN · 2004 to 2021
$4.6M
Assembly of Picornaviral Replication ComplexesR37AI059130 · NIAID · COLORADO STATE UNIVERSITY · PI Olve Breien Peersen · 2023 to 2026
$1.5M
Assembly of Picornaviral Replication ComplexesR56AI059130 · NIAID · COLORADO STATE UNIVERSITY · PI PEERSEN, OLVE BREIEN · 2009 to 2009
$324k
NIAID NIH HHS R01 AI059130NIAID NIH HHS R37 AI059130NIAID NIH HHS R56 AI059130
6 · The paper itself

Abstract

The ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. We demonstrate here that Favipiravir predominantly exerts an antiviral effect through lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.

Indexed as

AmidesAnimalsAntiviral AgentsBetacoronavirusChlorocebus aethiopsCoronavirus InfectionsCoronavirus RNA-Dependent RNA PolymeraseCOVID-19COVID-19 Drug TreatmentModels, MolecularMutagenesisPandemicsPneumonia, ViralPyrazinesRNA-Dependent RNA PolymeraseRNA, ViralAmidesAntiviral AgentsCoronavirus RNA-Dependent RNA PolymerasefavipiravirNSP12 protein, SARS-CoV-2PyrazinesRNA-Dependent RNA PolymeraseRNA, ViralT 1105Viral Nonstructural Proteins

Identifiers

PMID32943628
PMCPMC7499305
OpenAlexW3087747244

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.