Evidence map›Paper›PMID 33903110›Full record

ArticleAntimicrobial agents and chemotherapy2021

Overcoming Culture Restriction for SARS-CoV-2 in Human Cells Facilitates the Screening of Compounds Inhibiting Viral Replication.

Santseharay Ramirez, Carlota Fernandez-Antunez, Andrea Galli, Alexander Underwood, Long V Pham, Line A Ryberg, Shan Feng, Martin S Pedersen, Lotte S Mikkelsen, Sandrine Belouzard and 6 more

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
4.7field-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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.

  1. Pooled it
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  10. Mycophenolic acid treatment drives the emergence of novel SARS-CoV-2 variants.Proceedings of the National Academy of Sciences of the United States of America · 2025
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1 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

16 authors at 2 institutions in 2 countries.

Santseharay RamirezCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Carlota Fernandez-AntunezCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Andrea GalliCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Alexander UnderwoodCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Long V PhamCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Line A RybergCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Shan FengCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Martin S PedersenCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Lotte S MikkelsenCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Sandrine BelouzardUniversity of Lille, CNRS, Inserm, CHU Lille, Lille, France.
Jean DubuissonUniversity of Lille, CNRS, Inserm, CHU Lille, Lille, France.
Christina SølundCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Nina WeisDepartment of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Judith M GottweinCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Ulrik FahnøeCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
Jens BukhCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark.
University of Copenhagen · DKCentre National de la Recherche Scientifique · FR

Funding

Candys FoundationKøbmand I Odense Johan og Hanne Weimann Født Seedorffs Legat (Købmand i Odense Johann og Hanne Weimann født Seedorffs Legat)Ministry of Science, Innovation and Higher Education | Danish Agency for Science and Higher Education (Danish Agency for Science, Technology and Innovation)Novo Nordisk Fonden (NNF)Sundhed og Sygdom, Det Frie Forskningsråd (FSS, DFF)
6 · The paper itself

Abstract

Efforts to mitigate the coronavirus disease 2019 (COVID-19) pandemic include the screening of existing antiviral molecules that could be repurposed to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although SARS-CoV-2 replicates and propagates efficiently in African green monkey kidney (Vero) cells, antivirals such as nucleos(t)ide analogs (NUCs) often show decreased activity in these cells due to inefficient metabolization. SARS-CoV-2 exhibits low viability in human cells in culture. Here, serial passages of a SARS-CoV-2 isolate (original-SARS2) in the human hepatoma cell clone Huh7.5 led to the selection of a variant (adapted-SARS2) with significantly improved infectivity in human liver (Huh7 and Huh7.5) and lung cancer (unmodified Calu-1 and A549) cells. The adapted virus exhibited mutations in the spike protein, including a 9-amino-acid deletion and 3 amino acid changes (E484D, P812R, and Q954H). E484D also emerged in Vero E6-cultured viruses that became viable in A549 cells. Original and adapted viruses were susceptible to scavenger receptor class B type 1 (SR-B1) receptor blocking, and adapted-SARS2 exhibited significantly less dependence on ACE2. Both variants were similarly neutralized by COVID-19 convalescent-phase plasma, but adapted-SARS2 exhibited increased susceptibility to exogenous type I interferon. Remdesivir inhibited original- and adapted-SARS2 similarly, demonstrating the utility of the system for the screening of NUCs. Among the tested NUCs, only remdesivir, molnupiravir, and, to a limited extent, galidesivir showed antiviral effects across human cell lines, whereas sofosbuvir, ribavirin, and favipiravir had no apparent activity. Analogously to the emergence of spike mutations

Indexed as

COVID-19SARS-CoV-2Antiviral AgentsChlorocebus aethiopsHumansPandemicsSpike Glycoprotein, CoronavirusVirus ReplicationAntiviral AgentsSpike Glycoprotein, CoronavirusA549 cellscoronavirusCOVID-19galidesivirHuh7.5 cellsmolnupiravirnucleotide analogsremdesivirsofosbuvirvirus evolution

Identifiers

PMID33903110
PMCPMC8406809
OpenAlexW3158782644

What OpenQuestion holds

Textmetadata
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.