Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.

Cell
Qihui WangJianxun Qi

Abstract

The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.

References

Sep 22, 2001·Acta Crystallographica. Section D, Biological Crystallography·R J Read
Apr 12, 2003·The New England Journal of Medicine·Thomas G KsiazekUNKNOWN SARS Working Group
Feb 3, 2004·The Journal of Biological Chemistry·Paul TowlerMichael W Pantoliano
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
May 18, 2005·Proceedings of the National Academy of Sciences of the United States of America·Heike HofmannStefan Pöhlmann
May 24, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Susan S ChiuJ S M Peiris
Jun 9, 2005·Biochemical and Biophysical Research Communications·Jinzhu DuanGang Jin
Feb 10, 2009·Nature Reviews. Microbiology·Lanying DuShibo Jiang
Feb 26, 2009·The Journal of Infectious Diseases·Geoffrey J GorseKristin L Nichol
Nov 7, 2009·Clinics in Laboratory Medicine·Brigitte A Wevers, Lia van der Hoek
Nov 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kailang WuFang Li
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Mar 1, 2012·Frontiers in Microbiology·Fumihiro Taguchi, Asuka Hirai-Yuki
Oct 19, 2012·The New England Journal of Medicine·Ali M ZakiRon A M Fouchier
Dec 22, 2012·BMC Infectious Diseases·Monika JevšnikMiroslav Petrovec
Jan 23, 2013·The Pediatric Infectious Disease Journal·Andréanne JeanMakeda Semret
Oct 18, 2013·Molecular Biology and Evolution·Koichiro TamuraSudhir Kumar
Apr 23, 2014·Nucleic Acids Research·Xavier Robert, Patrice Gouet
Jun 5, 2014·The New England Journal of Medicine·Esam I AzharTariq A Madani
Jul 29, 2015·Nature Communications·Lingshu WangBarney S Graham
Nov 10, 2015·Nature Medicine·Vineet D MenacheryRalph S Baric
Jul 30, 2016·Antiviral Research·Qihui WangGeorge F Gao
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor
Oct 27, 2017·Protein Science : a Publication of the Protein Society·Christopher J WilliamsDavid C Richardson
Dec 6, 2019·Journal of Virology·Vineet D MenacheryRalph S Baric
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Jan 28, 2020·Lancet·Chen WangGeorge F Gao
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Feb 23, 2020·Lancet·Shibo JiangDeyin Guo

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Citations

May 5, 2020·Microbial Biotechnology·Harald Brüssow
May 14, 2020·American Journal of Physiology. Endocrinology and Metabolism·Afif Nakhleh, Naim Shehadeh
Jun 9, 2020·Clinical Science·Katharina LanzaAna Cristina Simões E Silva
May 18, 2020·The FEBS Journal·Alexander WlodawerMariusz Jaskolski
May 3, 2020·ASAIO Journal : a Peer-reviewed Journal of the American Society for Artificial Internal Organs·Keshava RajagopalMarvin J Slepian
Jul 8, 2020·International Journal of Molecular Sciences·Irene RamosDolores Pérez-Sala
Jul 16, 2020·Journal of Evaluation in Clinical Practice·Jeffrey K AronsonJon Williamson
Jul 15, 2020·ELife·Roger Pique-RegiNardhy Gomez-Lopez
Jun 15, 2020·Allergy·Carmen RiggioniCezmi A Akdis
Jul 31, 2020·ELife·Shumayila Khan, James Gomes
Aug 5, 2020·Indian Journal of Gastroenterology : Official Journal of the Indian Society of Gastroenterology·Ashish KumarAbhishyant Srivastava
Aug 14, 2020·Andrologia·Osamah BatihaEmad Alsharu
Aug 11, 2020·Médecine sciences : M/S·Erwan SallardÉtienne Decroly
Aug 26, 2020·Experimental Biology and Medicine·Cankat KaraNihal Beldüz Kara
Sep 5, 2020·Seminars in Liver Disease·Maria J Lizardo-ThiebaudNalu Navarro-Alvarez
Sep 6, 2020·Nucleic Acids Research·Ragul GowthamanBrian G Pierce
Sep 15, 2020·Briefings in Bioinformatics·Wenzhong Yang, Guangxu Jin
Sep 15, 2020·Veterinary Research Communications·Rubal SinglaBikash Medhi
Sep 17, 2020·Journal of Biomolecular Structure & Dynamics·Mohamed A HelalNagwa El-Badri
Sep 24, 2020·Expert Review of Vaccines·Leonard MoiseAnne S De Groot
Sep 24, 2020·Journal of Racial and Ethnic Health Disparities·Nicole PhillipsHarlan P Jones
Jun 20, 2020·EMBO Molecular Medicine·Anastasia PolycarpouSteven Sacks
Jul 19, 2020·Nature Communications·Xiaoyi FanXinzheng Zhang
Aug 6, 2020·Frontiers in Public Health·Waquar AhsanShahnaz Sultana
Jun 23, 2020·Clinical Hemorheology and Microcirculation·F JungJ-H Küpper
Aug 9, 2020·International Journal of Environmental Research and Public Health·Hossein HozhabriMeysam Sarshar

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Datasets Mentioned

BETA
BAJ21180
JX869050
AVP78042.1

Methods Mentioned

BETA
flow cytometry
fluorescence microscopy
confocal microscopy
size exclusion chromatography
glycosylation
surface plasmon resonance
chip
transfection
flow
FACS

Software Mentioned

Phenix
BIAcore® 8K Evaluation
MolProbity
HKL2000
MEGA
Pymol
BIAcore®
FlowJo

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