Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.
COVID-19
/ metabolism
Conserved Sequence
Coronavirus Nucleocapsid Proteins
/ genetics
Cryoelectron Microscopy
Host Microbial Interactions
Humans
Mitochondrial Membrane Transport Proteins
/ genetics
Mitochondrial Precursor Protein Import Complex Proteins
Phosphoproteins
/ genetics
Protein Conformation
Protein Interaction Maps
Severe acute respiratory syndrome-related coronavirus
/ metabolism
SARS-CoV-2
/ metabolism
Severe Acute Respiratory Syndrome
/ metabolism
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
04 12 2020
04 12 2020
Historique:
received:
24
09
2020
accepted:
12
10
2020
pubmed:
17
10
2020
medline:
29
12
2020
entrez:
16
10
2020
Statut:
ppublish
Résumé
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.
Identifiants
pubmed: 33060197
pii: science.abe9403
doi: 10.1126/science.abe9403
pmc: PMC7808408
pii:
doi:
Substances chimiques
Coronavirus Nucleocapsid Proteins
0
Mitochondrial Membrane Transport Proteins
0
Mitochondrial Precursor Protein Import Complex Proteins
0
Phosphoproteins
0
TOMM70 protein, human
0
nucleocapsid phosphoprotein, SARS-CoV-2
0
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : T32 AI060537
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007618
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI122747
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA239333
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI128214
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122481
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI063302
Pays : United States
Organisme : NIAID NIH HHS
ID : P50 AI150476
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12016/2
Pays : United Kingdom
Organisme : The Laboratory for Genomics Research, which is a collaboration between the Innovative Genomics Institute of UC Berkeley/UCSF and GlaxoSmithKline
ID : 133122P
Pays : International
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/J014443/1
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R01 GM024485
Pays : United States
Organisme : NIAID NIH HHS
ID : F30 AI143401
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI120694
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008284
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_19026
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : R01 HG008742
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135990
Pays : United States
Organisme : NIGMS NIH HHS
ID : F32 GM137463
Pays : United States
Organisme : Wellcome Trust
ID : 201366/Z/16/Z
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R01 NS089713
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118099
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009979
Pays : United States
Organisme : Medical Research Council
ID : MR/V03541X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00018/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : P01 AI120943
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135972
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12014/2
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : K99 GM138753
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA239336
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143292
Pays : United States
Investigateurs
Tristan W Owens
(TW)
Meghna Gupta
(M)
Sergei Pourmal
(S)
Erron W Titus
(EW)
Caleigh M Azumaya
(CM)
Christian Billesbølle
(C)
Axel F Brilot
(AF)
Melody G Campbell
(MG)
Amy Diallo
(A)
Miles Sasha Dickinson
(MS)
Devan Diwanji
(D)
Nadia Herrera
(N)
Nick Hoppe
(N)
Huong T Kratochvil
(HT)
Yanxin Liu
(Y)
Gregory E Merz
(GE)
Michelle Moritz
(M)
Henry C Nguyen
(HC)
Carlos Nowotny
(C)
Cristina Puchades
(C)
Alexandrea N Rizo
(AN)
Ursula Schulze-Gahmen
(U)
Amber M Smith
(AM)
Ming Sun
(M)
Iris D Young
(ID)
Jianhua Zhao
(J)
Daniel Asarnow
(D)
Justin Biel
(J)
Alisa Bowen
(A)
Julian R Braxton
(JR)
Jen Chen
(J)
Cynthia M Chio
(CM)
Un Seng Chio
(US)
Ishan Deshpande
(I)
Loan Doan
(L)
Bryan Faust
(B)
Sebastian Flores
(S)
Mingliang Jin
(M)
Kate Kim
(K)
Victor L Lam
(VL)
Fei Li
(F)
Junrui Li
(J)
Yen-Li Li
(YL)
Yang Li
(Y)
Xi Liu
(X)
Megan Lo
(M)
Kyle E Lopez
(KE)
Arthur A Melo
(AA)
Frank R Moss
(FR)
Phuong Nguyen
(P)
Joana Paulino
(J)
Komal Ishwar Pawar
(KI)
Jessica K Peters
(JK)
Thomas H Pospiech
(TH)
Maliheh Safari
(M)
Smriti Sangwan
(S)
Kaitlin Schaefer
(K)
Paul V Thomas
(PV)
Aye C Thwin
(AC)
Raphael Trenker
(R)
Eric Tse
(E)
Tsz Kin Martin Tsui
(TKM)
Feng Wang
(F)
Natalie Whitis
(N)
Zanlin Yu
(Z)
Kaihua Zhang
(K)
Yang Zhang
(Y)
Fengbo Zhou
(F)
Donovan Trinidad
(D)
David A Agard
(DA)
Yifan Cheng
(Y)
James S Fraser
(JS)
Adam Frost
(A)
Natalia Jura
(N)
Tanja Kortemme
(T)
Aashish Manglik
(A)
Daniel R Southworth
(DR)
Robert M Stroud
(RM)
Oren S Rosenberg
(OS)
Kliment A Verba
(KA)
Joana Damas
(J)
Graham M Hughes
(GM)
Kathleen C Keough
(KC)
Corrie A Painter
(CA)
Nicole S Persky
(NS)
Marco Corbo
(M)
Bodgan Kirilenko
(B)
Michael Hiller
(M)
Klaus-Peter Koepfli
(KP)
Irene Kaplow
(I)
Morgan Wirthlin
(M)
Andreas R Pfenning
(AR)
Huabin Zhao
(H)
Diane P Genereux
(DP)
Ross Swofford
(R)
Abigail Lind
(A)
Katherine S Pollard
(KS)
Oliver A Ryderq
(OA)
Martin T Nweeia
(MT)
Jennifer Meadows
(J)
Michael Dong
(M)
Ola Wallerman
(O)
Vikki Marinescu
(V)
Kerstin Lindblad-Toh
(K)
David A Ray
(DA)
Sarahjane Power
(S)
Emma C Teeling
(EC)
Gaurav Chauhan
(G)
Shirley Xue Li
(SX)
Elinor K Karlsson
(EK)
Harris A Lewin
(HA)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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