학술논문

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms
Document Type
article
Author
Gordon, David EHiatt, JosephBouhaddou, MehdiRezelj, Veronica VUlferts, SvenjaBraberg, HannesJureka, Alexander SObernier, KirstenGuo, Jeffrey ZBatra, JyotiKaake, Robyn MWeckstein, Andrew ROwens, Tristan WGupta, MeghnaPourmal, SergeiTitus, Erron WCakir, MerveSoucheray, MargaretMcGregor, MichaelCakir, ZeynepJang, GwendolynO’Meara, Matthew JTummino, Tia AZhang, ZiyangFoussard, HeleneRojc, AjdaZhou, YuanKuchenov, DmitryHüttenhain, RuthXu, JieweiEckhardt, ManonSwaney, Danielle LFabius, Jacqueline MUmmadi, ManishaTutuncuoglu, BerilRathore, UjjwalModak, MayaHaas, PaigeHaas, Kelsey MNaing, Zun Zar ChiPulido, Ernst HShi, YingBarrio-Hernandez, InigoMemon, DanishPetsalaki, EiriniDunham, AlistairMarrero, Miguel CorreaBurke, DavidKoh, CassandraVallet, ThomasSilvas, Jesus AAzumaya, Caleigh MBillesbølle, ChristianBrilot, Axel FCampbell, Melody GDiallo, AmyDickinson, Miles SashaDiwanji, DevanHerrera, NadiaHoppe, NickKratochvil, Huong TLiu, YanxinMerz, Gregory EMoritz, MichelleNguyen, Henry CNowotny, CarlosPuchades, CristinaRizo, Alexandrea NSchulze-Gahmen, UrsulaSmith, Amber MSun, MingYoung, Iris DZhao, JianhuaAsarnow, DanielBiel, JustinBowen, AlisaBraxton, Julian RChen, JenChio, Cynthia MChio, Un SengDeshpande, IshanDoan, LoanFaust, BryanFlores, SebastianJin, MingliangKim, KateLam, Victor LLi, FeiLi, JunruiLi, Yen-LiLi, YangLiu, XiLo, MeganLopez, Kyle EMelo, Arthur AMoss, Frank RNguyen, PhuongPaulino, JoanaPawar, Komal IshwarPeters, Jessica K
Source
Science. 370(6521)
Subject
Biological Sciences
Bioinformatics and Computational Biology
Infectious Diseases
Prevention
Emerging Infectious Diseases
Pneumonia
Lung
Pneumonia & Influenza
Vaccine Related
Genetics
Biodefense
Infection
Generic health relevance
Good Health and Well Being
COVID-19
Conserved Sequence
Coronavirus Nucleocapsid Proteins
Cryoelectron Microscopy
Host Microbial Interactions
Humans
Mitochondrial Membrane Transport Proteins
Mitochondrial Precursor Protein Import Complex Proteins
Phosphoproteins
Protein Conformation
Protein Interaction Maps
Severe acute respiratory syndrome-related coronavirus
SARS-CoV-2
Severe Acute Respiratory Syndrome
QCRG Structural Biology Consortium
Zoonomia Consortium
General Science & Technology
Language
Abstract
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.