Evidence map›Paper›PMID 41279303›Full record

ArticlebioRxiv : the preprint server for biology2025

Template switching by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir.

Asif Rakib, Arnab Das, Subhas C Bera, Pim P B America, Misha Klein, Thomas K Anderson, John C Marecki, Bing Wang, Eline Bogers, Joy Y Feng and 9 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Asif RakibDepartment of Physics and Astronomy, and LaserLaB Amsterdam, Vrije Universiteit Amsterdam, De Boelelaan 1100, 1081 HZ, Amsterdam, the Netherlands.
Arnab DasDepartment of Physics and Astronomy, and LaserLaB Amsterdam, Vrije Universiteit Amsterdam, De Boelelaan 1100, 1081 HZ, Amsterdam, the Netherlands.
Subhas C BeraJunior Research Group 2, Interdisciplinary Center for Clinical Research, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Cauerstr. 3, 91058 Erlangen, Germany.ORCID 0000-0002-4168-1805
Pim P B AmericaDepartment of Physics and Astronomy, and LaserLaB Amsterdam, Vrije Universiteit Amsterdam, De Boelelaan 1100, 1081 HZ, Amsterdam, the Netherlands.
Misha KleinDepartment of Physics and Astronomy, and LaserLaB Amsterdam, Vrije Universiteit Amsterdam, De Boelelaan 1100, 1081 HZ, Amsterdam, the Netherlands.ORCID 0000-0001-8677-9710
Thomas K AndersonDepartment of Biochemistry and Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706, USA.
John C MareckiDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Bing WangDepartment of Microbiology and The Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA.
Eline BogersDepartment of Physics and Astronomy, and LaserLaB Amsterdam, Vrije Universiteit Amsterdam, De Boelelaan 1100, 1081 HZ, Amsterdam, the Netherlands.
Joy Y FengGilead Sciences, Inc., Foster City, CA 94404, USA.
John P BilelloGilead Sciences, Inc., Foster City, CA 94404, USA.
Flávia S PapiniJunior Research Group 2, Interdisciplinary Center for Clinical Research, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Cauerstr. 3, 91058 Erlangen, Germany.
Quinte SmitskampDepartment of Physics and Astronomy, and LaserLaB Amsterdam, Vrije Universiteit Amsterdam, De Boelelaan 1100, 1081 HZ, Amsterdam, the Netherlands.
Jamie J ArnoldDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Irina ArtsimovitchDepartment of Microbiology and The Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA.
Robert N KirchdoerferDepartment of Biochemistry and Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Craig E CameronDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Kevin D RaneyDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
David DulinDepartment of Physics and Astronomy, and LaserLaB Amsterdam, Vrije Universiteit Amsterdam, De Boelelaan 1100, 1081 HZ, Amsterdam, the Netherlands.ORCID 0000-0003-4209-0377

Funding

Research Project 1: Coronavirus antiviral lead development and combination testingU19AI171292 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S, WILLSON, TIMOTHY M · 2022 to 2022
$65.5M
Mechnanism of transcript elongation control by RfaHR01GM067153 · NIGMS · OHIO STATE UNIVERSITY · PI IRINA ARTSIMOVITCH · 2003 to 2026
$8.0M
Coronavirus Genome ReplicationR01AI161841 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Jamie Jon Arnold, CRAIG E. CAMERON · 2021 to 2026
$3.4M
Coronavirus RNA synthesis by multicomponent protein machinesR01AI158463 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KIRCHDOERFER, ROBERT N · 2020 to 2025
$2.1M
NIAID NIH HHS R01 AI158463NIAID NIH HHS R01 AI161841NIAID NIH HHS U19 AI171292NIGMS NIH HHS R01 GM067153
6 · The paper itself

Abstract

Polymerase template switching is an essential mechanism in coronaviruses (CoVs) that enables both sub-genomic (sg) RNA synthesis and increases genomic diversity via RNA recombination. Despite its importance, the molecular mechanism of CoV polymerase template switching remains unclear. Using magnetic tweezers, we show that the CoV non-structural protein (nsp) 13-helicase drives polymerase template switching, followed by copy-back RNA synthesis. This activity requires nsp13-helicase ATPase activity and a duplex RNA downstream of the CoV polymerase. This novel function of nsp13-helicase is targeted by the nucleotide analogs remdesivir and molnupiravir, whose incorporation in the nascent strand increases CoV polymerase template switching probability, leading to defective RNA production. We propose a novel mechanism of action where incorporation of these analogs dramatically reduces full length genome copy number by stimulating polymerase template switching. Our study further demonstrates nsp13-helicase's central role in CoV replication and how this enzyme function can be indirectly targeted by analogs.

Identifiers

PMID41279303
PMCPMC12632558

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.