Proteomics of SARS-CoV-2-infected host cells reveals therapy targets.

Nature
Denisa BojkovaChristian Münch

Abstract

A new coronavirus was recently discovered and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection with SARS-CoV-2 in humans causes coronavirus disease 2019 (COVID-19) and has been rapidly spreading around the globe1,2. SARS-CoV-2 shows some similarities to other coronaviruses; however, treatment options and an understanding of how SARS-CoV-2 infects cells are lacking. Here we identify the host cell pathways that are modulated by SARS-CoV-2 and show that inhibition of these pathways prevents viral replication in human cells. We established a human cell-culture model for infection with a clinical isolate of SARS-CoV-2. Using this cell-culture system, we determined the infection profile of SARS-CoV-2 by translatome3 and proteome proteomics at different times after infection. These analyses revealed that SARS-CoV-2 reshapes central cellular pathways such as translation, splicing, carbon metabolism, protein homeostasis (proteostasis) and nucleic acid metabolism. Small-molecule inhibitors that target these pathways prevented viral replication in cells. Our results reveal the cellular infection profile of SARS-CoV-2 and have enabled the identification of drugs that inhibit viral replication. We anticipate tha...Continue Reading

References

Aug 2, 2003·Lancet·J CinatlH W Doerr
Mar 28, 2008·Journal of Virology·Benjamin W NeumanPeter Kuhn
Jun 21, 2008·Journal of Gastroenterology and Hepatology·Paul Martin, Donald M Jensen
May 5, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hong Peng JiaPaul B McCray
Oct 20, 2009·Nature Structural & Molecular Biology·Wataru KamitaniShinji Makino
Mar 14, 2014·Transplant Infectious Disease : an Official Journal of the Transplantation Society·J R MarcelinUNKNOWN Mayo Clinic Hematology/Oncology and Transplant Infectious Diseases Services
Aug 28, 2015·Journal of Virology·Hui Hui WongFrédéric Bard
Jun 28, 2016·Nature Methods·Stefka TyanovaJürgen Cox
Feb 6, 2017·Methods in Molecular Biology·Guanming Wu, Robin Haw
Jul 1, 2017·Frontiers in Molecular Biosciences·Yihong YeDi Xia
Apr 17, 2018·Molecular Cell·Constantin CretuVladimir Pena
Jul 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Guido A GualdoniJohannes Stöckl
Nov 6, 2018·Nucleic Acids Research·Yasset Perez-RiverolJuan Antonio Vizcaíno
Apr 2, 2019·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Jiantao ZhangJun Wang
May 28, 2019·Current Opinion in Virology·Andrea J Pruijssers, Mark R Denison
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Feb 2, 2020·Drug Discovery Today·Thanigaimalai PillaiyarManoj Manickam
Feb 3, 2020·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Shi ZhaoMaggie H Wang
Feb 23, 2020·Clinical and Translational Medicine·Jun SheYuanlin Song
Mar 4, 2020·JAMA : the Journal of the American Medical Association·Barnaby Edward YoungUNKNOWN Singapore 2019 Novel Coronavirus Outbreak Research Team
Mar 7, 2020·Gastroenterology·Fei XiaoHong Shan

❮ Previous
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Citations

May 2, 2020·Transplant International : Official Journal of the European Society for Organ Transplantation·Marzuq BillahSamira S Farouk
Jun 6, 2020·American Journal of Physiology. Endocrinology and Metabolism·Xiaoling CaoWenbin Tan
May 20, 2020·Omics : a Journal of Integrative Biology·Sandipan Ray, Sanjeeva Srivastava
Jun 28, 2020·Molecular & Cellular Proteomics : MCP·Jana ZechaBernhard Kuster
Sep 26, 2020·Frontiers in Cell and Developmental Biology·Andres Mariano Alonso, Luis Diambra
Jun 26, 2020·Frontiers in Cell and Developmental Biology·Jie YuXianqun Fan
Aug 21, 2020·Cell Death & Disease·Allan SauvatGuido Kroemer
Sep 26, 2020·Frontiers in Immunology·Juan Garcia-RevillaAntonio Boza-Serrano
Jul 19, 2020·Tropical Animal Health and Production·Jaka Jakob HodnikJože Starič
Aug 6, 2020·Diagnostics·Katie-May McLaughlinJindrich Cinatl
Jul 24, 2020·Nature Reviews. Molecular Cell Biology·Sandipan Ray, Akhilesh B Reddy
Jul 22, 2020·Emerging Microbes & Infections·Sofia AppelbergUjjwal Neogi
Jul 23, 2020·Nature Metabolism·Janelle S Ayres
Oct 1, 2020·International Journal of Molecular Sciences·Rajneesh SrivastavaSarath Chandra Janga
Sep 11, 2020·Nature Genetics·Jennifer A FlynnTing Wang
Jun 25, 2020·International Journal of Molecular Sciences·Tuna ToptanMarek Widera
Aug 7, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Julie A Bastarache
Sep 25, 2020·Circulation·Antoine RauchUNKNOWN Lille Covid Research Network(LICORNE)
Sep 10, 2020·Nature·Yaara FinkelNoam Stern-Ginossar
Jul 17, 2020·International Journal of Molecular Sciences·Markus BlaessHans-Peter Deigner
Oct 18, 2020·Nature Communications·Subash AdhikariMark S Baker
Oct 22, 2020·Viruses·Aleksandr IanevskiDenis E Kainov
Sep 24, 2020·Cardiovascular Research·Denisa BojkovaStefanie Dimmeler
Nov 22, 2020·Journal of Translational Medicine·Antonio PaoliMassimiliano Caprio
Dec 3, 2020·Pharmaceuticals·Martin D Bleasel, Gregory M Peterson
Nov 26, 2020·Proteomics·Lucia Grenga, Jean Armengaud
Dec 7, 2020·Briefings in Bioinformatics·Francesca P CarusoMichele Ceccarelli
Dec 11, 2020·PLoS Pathogens·Katarzyna PancerKrzysztof Pyrc
Dec 31, 2020·Critical Reviews in Clinical Laboratory Sciences·Baoxu LinXiaosong Qin
Jan 8, 2021·Tissue Engineering. Part C, Methods·Vera M PietersAlison P McGuigan
Jan 11, 2021·Briefings in Bioinformatics·Shasha LiChenyang Lu
Jan 14, 2021·Journal of Biomedical Science·Ioannis P TrougakosMeletios A Dimopoulos

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Methods Mentioned

BETA
PCR

Clinical Trials Mentioned

NCT04356677

Software Mentioned

MaxQuant
Excel
Python
Perseus
EnrichmentMap
Reactome
OriginPro
Proteome Discoverer
Cytoscape
ReactomeFI

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