Evidence map›Paper›PMID 37134108›Full record

ArticlePLoS pathogens2023

An ACAT inhibitor suppresses SARS-CoV-2 replication and boosts antiviral T cell activity.

Peter A C Wing, Nathalie M Schmidt, Rory Peters, Maximilian Erdmann, Rachel Brown, Hao Wang, Leo Swadling, COVIDsortium Investigators, Joseph Newman, Nazia Thakur and 9 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04318314 (COVID-19), which is not on this map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.0field-weighted citation impact, top 9% 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.

NCT04318314 unknown statusnot on this map

COVID-19: Healthcare Worker Bioresource: Immune Protection and Pathogenesis in SARS-CoV-2

Typeobservational_patient_registrySponsorUniversity College, LondonRan2020 to 2022Enrolled731ConditionsHealth Care Worker Patient Transmission, Coronavirus, Coronavirus Infections, Immunological AbnormalityArmsCOPAN swabbing and blood sample collection
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 18 citations in OpenAlex.

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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

19 authors at 8 institutions in 4 countries.

Peter A C WingChinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, United Kingdom.
Nathalie M SchmidtDivision of Infection and Immunity and Institute of Immunity and Transplantation, UCL, London, United Kingdom.
Rory PetersNuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Maximilian ErdmannSchool of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
Rachel BrownDivision of Infection and Immunity and Institute of Immunity and Transplantation, UCL, London, United Kingdom.
Hao WangDepartments of Molecular Medicine and Neuroscience, The Scripps Research Institute, San Diego, California, United States of America.
Leo SwadlingDivision of Infection and Immunity and Institute of Immunity and Transplantation, UCL, London, United Kingdom.
COVIDsortium Investigators
Joseph NewmanThe Pirbright Institute, Woking, United Kingdom.
Nazia ThakurThe Pirbright Institute, Woking, United Kingdom.
Kaho ShionoyaDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Sophie B MorganRespiratory Medicine Unit and National Institute for Health Research Oxford Biomedical Research Centre, Nuffield Department of Medicine, Experimental Medicine, University of Oxford, Oxford, United Kingdom.
Timothy Sc HinksRespiratory Medicine Unit and National Institute for Health Research Oxford Biomedical Research Centre, Nuffield Department of Medicine, Experimental Medicine, University of Oxford, Oxford, United Kingdom.
Koichi WatashiDepartment of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
Dalan BaileyThe Pirbright Institute, Woking, United Kingdom.
Scott B HansenUCL Queen Square Institute of Neurology, London, United Kingdom.
Andrew D DavidsonSchool of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
Mala K MainiDivision of Infection and Immunity and Institute of Immunity and Transplantation, UCL, London, United Kingdom.ORCID 0000-0001-6384-1462
Jane A McKeatingChinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-7229-5886
The Pirbright Institute · GBCentre for Immunity, Infection and Evolution · GBChinese Academy of Medical Sciences & Peking Union Medical College · CNUniversity of Bristol · GBTokyo University of Science · JPNational Institute for Health Research · GBScripps Research Institute · USUniversity of Oxford · GB

Funding

The role of lipid raft disruption in the activation of TREK-1 channels by anestheticsR01NS112534 · NINDS · UNIVERSITY OF FLORIDA · PI HANSEN, SCOTT B · 2019 to 2023
$2.2M
Biotechnology and Biological Sciences Research Council BBS/E/I/00007034Biotechnology and Biological Sciences Research Council BBS/E/I/00007038Biotechnology and Biological Sciences Research Council BBS/E/I/COV07001Medical Research Council MR/R022011/1Medical Research Council MR/T001313/1Medical Research Council MR/V027506/1Medical Research Council MR/W005611/1NINDS NIH HHS R01 NS112534Wellcome Trust 200838/Z/16/Z
6 · The paper itself

Abstract

The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, with early T cell responses and/or suppression of viraemia driving a favourable outcome. Recent studies uncovered a role for cholesterol metabolism in the SARS-CoV-2 life cycle and in T cell function. Here we show that blockade of the enzyme Acyl-CoA:cholesterol acyltransferase (ACAT) with Avasimibe inhibits SARS-CoV-2 pseudoparticle infection and disrupts the association of ACE2 and GM1 lipid rafts on the cell membrane, perturbing viral attachment. Imaging SARS-CoV-2 RNAs at the single cell level using a viral replicon model identifies the capacity of Avasimibe to limit the establishment of replication complexes required for RNA replication. Genetic studies to transiently silence or overexpress ACAT isoforms confirmed a role for ACAT in SARS-CoV-2 infection. Furthermore, Avasimibe boosts the expansion of functional SARS-CoV-2-specific T cells from the blood of patients sampled during the acute phase of infection. Thus, re-purposing of ACAT inhibitors provides a compelling therapeutic strategy for the treatment of COVID-19 to achieve both antiviral and immunomodulatory effects. Trial registration: NCT04318314.

Indexed as

Antiviral AgentsCOVID-19AcetamidesAcyltransferasesHumansSARS-CoV-2SulfonamidesT-LymphocytesAcetamidesAcyltransferasesAntiviral AgentsavasimibeSulfonamides

Identifiers

PMID37134108
PMCPMC10202285
OpenAlexW4367835028

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.