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Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

David E GordonJoseph HiattMehdi BouhaddouVeronica V RezeljSvenja UlfertsHannes BrabergAlexander S JurekaKirsten ObernierJeffrey Z GuoJyoti BatraRobyn M KaakeAndrew R WecksteinTristan W OwensMeghna GuptaSergei PourmalErron W TitusMerve CakirMargaret SoucherayMichael J McGregorZeynep CakirGwendolyn M JangMatthew J O'MearaTia A TumminoZiyang ZhangHelene FoussardAjda RojcYuan ZhouDmitry KuchenovRuth HüttenhainJiewei XuManon EckhardtDanielle L SwaneyJacqueline M FabiusManisha UmmadiBeril TutuncuogluUjjwal RathoreMaya ModakPaige HaasKelsey M HaasZun Zar Chi NaingErnst H PulidoYing ShiInigo Barrio-HernandezDanish MemonEirini PetsalakiAlistair S DunhamMiguel Correa MarreroDavid Francis BurkeCassandra KohThomas ValletJesus A SilvasCaleigh M AzumayaChristian B BillesbølleAxel F BrilotMelody G CampbellAmy DialloMiles Sasha DickinsonDevan DiwanjiNadia HerreraNicholas HoppeHuong T KratochvilYanxin LiuGregory E MerzMichelle MoritzHenry C NguyenCarlos A NowotnyCristina PuchadesAlexandrea N RizoUrsula Schulze-GahmenAmber M SmithMing SunIris D YoungJianhua ZhaoDaniel AsarnowJustin T BielAlisa BowenJulian R BraxtonJen ChenCynthia M ChioUn Seng ChioIshan DeshpandeLoan DoanBryan FaustSebastian FloresMingliang JinSun Kyung KimVictor L LamFei LiJunrui LiGrant J JensenYang LiXi LiuMegan LoKyle E LopezArthur A MeloFrank R MossPhuong NguyenJoana PaulinoKomal Ishwar PawarJessica K PetersThomas H PospiechMaliheh SafariSmriti SangwanKaitlin SchaeferPaul V ThomasAye C ThwinRaphael TrenkerEric TseTsz Kin Martin TsuiFeng WangNatalie WhitisZanlin YuKaihua ZhangSunny ZhangFengbo ZhouDaniel J Saltzbergnull nullAnthony J HodderAmber S Shun-ShionDaniel M WilliamsKris M WhiteRomel RosalesThomas KehrerLisa MiorinElena MorenoArvind H PatelSuzannah J RihnMir Mubashir KhalidAlbert Vallejo-GraciaParinaz FozouniCamille R SimoneauTheodore L RothDavid WuMohd Anisul KarimMaya GhoussainiIan DunhamFrancesco BerardiSebastian WeigangMaxime ChazalJisoo ParkJames P LogueMarisa E McGrathStuart M WestonRobert E HauptC James HastieMatthew ElliottFiona BrownKerry A BurnessElaine ReidMark DorwardClare JohnsonStuart G WilkinsonAnna GeyerDaniel M GieselCarla BaillieSamantha RaggettHannah LeechRachel TothNicola GoodmanKathleen C KeoughAbigail L Lindnull nullReyna J KleshKafi R HemphillJared Carlson-StevermerJennifer OkiKevin HoldenTravis MauresKatherine S PollardAndrej SaliDavid A AgardYifan ChengBrian K ShoichetAdam FrostNatalia JuraTanja KortemmeAashish ManglikDaniel R SouthworthRobert M StroudDario R AlessiPaul DaviesMatthew B FriemannTrey IdekerCarmen AbateNolwenn JouvenetGeorg KochsBrian K ShoichetMelanie M OttMassimo PalmariniKevan M ShokatAdolfo García-SastreJeremy A RassenRobert GrosseOren S RosenbergKliment A VerbaChristopher F BaslerMarco VignuzziAndrew A PedenPedro BeltraoNevan J Krogan
Published in: Science (New York, N.Y.) (2020)
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.
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