Evidence map›Paper›PMID 38361624›Full record

ArticleiScience2024

Bioluminescence imaging reveals enhanced SARS-CoV-2 clearance in mice with combinatorial regimens.

Irfan Ullah, Fanny Escudie, Ivan Scandale, Zoela Gilani, Gabrielle Gendron-Lepage, Fleur Gaudette, Charles Mowbray, Laurent Fraisse, Renée Bazin, Andrés Finzi and 4 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

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  5. Proof-of-concept studies with a computationally designed MProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 3 countries.

Irfan UllahDepartment of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Fanny EscudieDrugs for Neglected Diseases Initiative, Geneva, Switzerland.
Ivan ScandaleDrugs for Neglected Diseases Initiative, Geneva, Switzerland.
Zoela GilaniDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
Gabrielle Gendron-LepageCentre de Recherche du CHUM, Montréal, QC H2X0A9, Canada.
Fleur GaudetteCentre de Recherche du CHUM, Montréal, QC H2X0A9, Canada.
Charles MowbrayDrugs for Neglected Diseases Initiative, Geneva, Switzerland.
Laurent FraisseDrugs for Neglected Diseases Initiative, Geneva, Switzerland.
Renée BazinHema-Quebec, Affaires Médicales et Innovation, Québec, QC G1V 5C3, Canada.
Andrés FinziCentre de Recherche du CHUM, Montréal, QC H2X0A9, Canada.
Walther MothesDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
Priti KumarDepartment of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Eric ChatelainDrugs for Neglected Diseases Initiative, Geneva, Switzerland.
Pradeep D UchilDepartment of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
Drugs for Neglected Diseases Initiative · CHYale University · USCentre Hospitalier de l’Université de Montréal · CAHéma-Québec · CAUniversité de Montréal · CA

Funding

Live imaging of SARS-CoV-2 infection in novel humanized miceR24OD026440 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BREHM, MICHAEL ALLEN, EMERSON, CHARLES P. · 2019 to 2022
$4.2M
Structure and Dynamics of the SARS-CoV-2 Spike ProteinR01AI163395 · NIAID · YALE UNIVERSITY · PI MOTHES, WALTHER H · 2021 to 2025
$4.1M
NIAID NIH HHS R01 AI163395NIH HHS R24 OD026440Wellcome Trust
6 · The paper itself

Abstract

Direct acting antivirals (DAAs) represent critical tools for combating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have escaped vaccine-elicited spike-based immunity and future coronaviruses with pandemic potential. Here, we used bioluminescence imaging to evaluate therapeutic efficacy of DAAs that target SARS-CoV-2 RNA-dependent RNA polymerase (favipiravir, molnupiravir) or main protease (nirmatrelvir) against Delta or Omicron VOCs in K18-hACE2 mice. Nirmatrelvir displayed the best efficacy followed by molnupiravir and favipiravir in suppressing viral loads in the lung. Unlike neutralizing antibody treatment, DAA monotherapy regimens did not eradicate SARS-CoV-2 in mice, but combining molnupiravir with nirmatrelvir exhibited superior additive efficacy and led to virus clearance. Furthermore, combining molnupiravir with caspase-1/4 inhibitor mitigated inflammation and lung pathology whereas combining molnupiravir with COVID-19 convalescent plasma demonstrated synergy, rapid virus clearance, and 100% survival. Thus, our study provides insights into

Indexed as

Optical imagingVirology

Identifiers

PMID38361624
PMCPMC10867665
OpenAlexW4391344409

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.