SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Cell
Markus HoffmannStefan Pöhlmann

Abstract

The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

References

Mar 26, 2005·The EMBO Journal·Wenhui LiMichael Farzan
May 18, 2005·Proceedings of the National Academy of Sciences of the United States of America·Heike HofmannStefan Pöhlmann
Jul 8, 2005·Nature·Yumiko ImaiJosef M Penninger
Jul 27, 2005·The Journal of Experimental Medicine·Jiang GuAnthony S-Y Leong
Aug 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Graham SimmonsPaul Bates
Sep 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Susanna K P LauKwok-Yung Yuen
Jan 24, 2006·Molecular and Cellular Biology·Tom S KimPeter S Nelson
May 21, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shiori HagaYukihito Ishizaka
Jul 16, 2010·Journal of Virology·Stephanie BertramStefan Pöhlmann
Aug 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·Yang YangFang Li
Feb 11, 2015·Antiviral Research·Yanchen ZhouGraham Simmons
Jun 28, 2016·Nature Reviews. Microbiology·Emmie de WitVincent J Munster
Aug 31, 2016·Annual Review of Medicine·Anthony R FehrStanley Perlman
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jung-Eun ParkTom Gallagher
Sep 20, 2017·Proceedings of the National Academy of Sciences of the United States of America·Wentao LiBerend-Jan Bosch
May 4, 2018·Molecular Biology and Evolution·Sudhir KumarKoichiro Tamura
Nov 11, 2018·Scientific Reports·Hannah Kleine-WeberStefan Pöhlmann
Aug 29, 2019·Der Internist·V M CormanM Witzenrath
Dec 4, 2019·Nature Structural & Molecular Biology·Young-Jun ParkDavid Veesler
Jan 25, 2020·The New England Journal of Medicine·Vincent J MunsterEmmie de Wit
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team

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Citations

Mar 28, 2020·Journal of Crohn's & Colitis·Giovanni Monteleone, Sandro Ardizzone
Apr 3, 2020·Vaccines·Jinyong ZhangQuanming Zou
Apr 4, 2020·Pediatric Pulmonology·Lael M YonkerT Bernard Kinane
Apr 4, 2020·Diabetic Medicine : a Journal of the British Diabetic Association·R C W Ma, R I G Holt
Apr 4, 2020·BMJ : British Medical Journal·Jeffrey K Aronson, Robin E Ferner
Mar 19, 2020·International Journal of Clinical Practice·George Thomson
Apr 8, 2020·Circulation Research·Akbarshakh Akhmerov, Eduardo Marban
Apr 7, 2020·American Journal of Hypertension·Ernesto L SchiffrinR Clinton Webb
Apr 16, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Vanesa PalauMaría José Soler
Apr 7, 2020·Journal of Medical Virology·Mushtaq HussainBasma Aziz
Apr 16, 2020·Circulation·Peter P LiuHongliang Li
Mar 29, 2020·QJM : Monthly Journal of the Association of Physicians·M R GoldsteinC W Graeber
Apr 5, 2020·Journal of Clinical Medicine·Pietro H GuzziFederico M Giorgi
Apr 17, 2020·Circulation. Cardiovascular Quality and Outcomes·Heather M AlgerChristine Rutan
Apr 18, 2020·Circulation Research·Venkatesh L MurthyRavi V Shah
Apr 20, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tiantian YanGuoan Lin
Mar 28, 2020·Journal of Gastroenterology and Hepatology·Sunny H WongJoseph Jy Sung
Apr 16, 2020·Stem Cells and Development·Robert Chunhua Zhao
Mar 11, 2020·Antimicrobial Agents and Chemotherapy·Miguel Angel Martinez
Apr 1, 2020·Nature·Jian ShangFang Li
Apr 11, 2020·Journal of Biomolecular Structure & Dynamics·Anwarul HasanMojtaba Falahati
Apr 23, 2020·Journal of Medical Microbiology·Timothy J J Inglis
Apr 25, 2020·The New England Journal of Medicine·Rajesh T GandhiCarlos Del Rio
Apr 28, 2020·Viral Immunology·José Valter Joaquim Silva JúniorEduardo Furtado Flores
Apr 30, 2020·Phytotherapy Research : PTR·Solomon HabtemariamSeyed Mohammad Nabavi
May 1, 2020·Journal of Cardiovascular Pharmacology and Therapeutics·Himanshu SankrityayanAnil Bhanudas Gaikwad
May 2, 2020·The New England Journal of Medicine·John A JarchoDavid P Harrington
May 2, 2020·The New England Journal of Medicine·Mandeep R MehraAmit N Patel
May 3, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Joseph A Roche, Renuka Roche
May 5, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Thomas Walther, Wolfgang M Kuebler
May 5, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Paul A WellingMatthew A Sparks
Apr 25, 2020·Journal of Biomolecular Structure & Dynamics·Rakesh S JoshiMahesh J Kulkarni
Apr 22, 2020·Gut·Maria EffenbergerHerbert Tilg
Apr 19, 2020·Gut·Markus F Neurath
May 7, 2020·Journal of Human Genetics·Kazuma KiyotaniYusuke Nakamura
Apr 7, 2020·The Journal of Clinical Investigation·Hamid Rabb

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Methods Mentioned

BETA
transfectability
Assay

Key Resources (RRID) Mentioned

CVCL_G654
CVCL_0023
CVCL_0168
CVCL_0609
CVCL_0060
CVCL_0336
CVCL_0025
CVCL_0574
CVCL_0391
CVCL_0421

Software Mentioned

MEGA7
GraphPad
ChemoStar Professional
GraphPad Prism

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