Evidence map›Paper›PMID 37731621›Full record

ArticleiScience2023

N4-hydroxycytidine, the active compound of Molnupiravir, promotes SARS-CoV-2 mutagenesis and escape from a neutralizing nanobody.

Arne Zibat, Xiaoxiao Zhang, Antje Dickmanns, Kim M Stegmann, Adrian W Dobbelstein, Halima Alachram, Rebecca Soliwoda, Gabriela Salinas, Uwe Groß, Dirk Görlich and 3 more

Abstract read
In one paragraph

Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. COVID-19 therapeutics.Clinical microbiology reviews · 2024
    Review
  6. The Tautomeric State ofACS central science · 2024
    Article
  7. Review
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.

Arne ZibatDepartment of Human Genetics, University Medical Center Göttingen, 37073 Göttingen, Germany.
Xiaoxiao ZhangDepartment of Mathematics and Technology, University of Applied Sciences Koblenz, 53424 Remagen, Germany.
Antje DickmannsDepartment of Molecular Oncology, Göttingen Center of Molecular Biosciences (GZMB), University Medical Center Göttingen, 37077 Göttingen, Germany.
Kim M StegmannDepartment of Molecular Oncology, Göttingen Center of Molecular Biosciences (GZMB), University Medical Center Göttingen, 37077 Göttingen, Germany.
Adrian W DobbelsteinMax Planck Institute for Biology, 72076 Tübingen, Germany.
Halima AlachramDepartment of Human Genetics, University Medical Center Göttingen, 37073 Göttingen, Germany.
Rebecca SoliwodaDepartment of Molecular Oncology, Göttingen Center of Molecular Biosciences (GZMB), University Medical Center Göttingen, 37077 Göttingen, Germany.
Gabriela SalinasNGS Integrative Genomics Core Unit, Department of Human Genetics, University Medical Center Göttingen, 37077 Göttingen, Germany.
Uwe GroßDepartment of Medical Microbiology and Virology, University Medical Center Göttingen, 37075 Göttingen, Germany.
Dirk GörlichMax Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany.
Maik KschischoDepartment of Mathematics and Technology, University of Applied Sciences Koblenz, 53424 Remagen, Germany.
Bernd WollnikDepartment of Human Genetics, University Medical Center Göttingen, 37073 Göttingen, Germany.
Matthias DobbelsteinDepartment of Molecular Oncology, Göttingen Center of Molecular Biosciences (GZMB), University Medical Center Göttingen, 37077 Göttingen, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

N4-hydroxycytidine (NHC), the active compound of the drug Molnupiravir, is incorporated into SARS-CoV-2 RNA, causing false base pairing. The desired result is an "error catastrophe," but this bears the risk of mutated virus progeny. To address this experimentally, we propagated the initial SARS-CoV-2 strain in the presence of NHC. Deep sequencing revealed numerous NHC-induced mutations and host-cell-adapted virus variants. The presence of the neutralizing nanobody Re5D06 selected for immune escape mutations, in particular p.E484K and p.F490S, which are key mutations of the Beta/Gamma and Omicron-XBB strains, respectively. With NHC treatment, nanobody resistance occurred two passages earlier than without. Thus, within the limitations of this purely

Indexed as

ImmunologyPharmaceutical scienceStructural biologyVirology

Identifiers

PMID37731621
PMCPMC10507161

What Socratic 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 Socratic graph.