Cell entry mechanisms of SARS-CoV-2

Proceedings of the National Academy of Sciences of the United States of America
Jian ShangFang Li

Abstract

A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is causing the global coronavirus disease 2019 (COVID-19) pandemic. Understanding how SARS-CoV-2 enters human cells is a high priority for deciphering its mystery and curbing its spread. A virus surface spike protein mediates SARS-CoV-2 entry into cells. To fulfill its function, SARS-CoV-2 spike binds to its receptor human ACE2 (hACE2) through its receptor-binding domain (RBD) and is proteolytically activated by human proteases. Here we investigated receptor binding and protease activation of SARS-CoV-2 spike using biochemical and pseudovirus entry assays. Our findings have identified key cell entry mechanisms of SARS-CoV-2. First, SARS-CoV-2 RBD has higher hACE2 binding affinity than SARS-CoV RBD, supporting efficient cell entry. Second, paradoxically, the hACE2 binding affinity of the entire SARS-CoV-2 spike is comparable to or lower than that of SARS-CoV spike, suggesting that SARS-CoV-2 RBD, albeit more potent, is less exposed than SARS-CoV RBD. Third, unlike SARS-CoV, cell entry of SARS-CoV-2 is preactivated by proprotein convertase furin, reducing its dependence on target cell proteases for entry. The high hACE2 binding affinity of the RBD, fur...Continue Reading

References

Apr 16, 2003·The New England Journal of Medicine·Nelson LeeJoseph J Y Sung
Apr 25, 2003·Lancet·J S M PeirisUNKNOWN SARS study group
Apr 3, 2007·Trends in Microbiology·David J Vigerust, Virginia L Shepherd
Dec 5, 2008·Microbiology and Molecular Biology Reviews : MMBR·Matthew Frieman, Ralph Baric
Feb 10, 2009·Nature Reviews. Microbiology·Lanying DuShibo Jiang
May 12, 2009·Nature Reviews. Microbiology·Stanley Perlman, Jason Netland
Nov 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·Suman R DasJonathan W Yewdell
Dec 20, 2011·Current Opinion in Virology·Meagan BollesRalph Baric
May 17, 2012·Viruses·Taylor Heald-Sargent, Tom Gallagher
Jul 21, 2012·Viruses·Sandrine BelouzardGary R Whittaker
Nov 22, 2013·Journal of Virology·Longping V TseGary R Whittaker
Dec 3, 2014·Virus Research·Jean Kaoru Millet, Gary R Whittaker
Sep 1, 2016·Annual Review of Virology·Fang Li
Oct 28, 2016·Microbiology and Molecular Biology Reviews : MMBR·Laura A VanBlarganTheodore C Pierson
Dec 13, 2016·Expert Opinion on Therapeutic Targets·Lanying DuShibo Jiang
Sep 28, 2018·Journal of Virology·Yuan ZhengFang Li
Jan 30, 2020·The New England Journal of Medicine·Qun LiZijian Feng
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
Mar 22, 2020·Proceedings of the National Academy of Sciences of the United States of America·Matthew HackbartSusan C Baker
Apr 1, 2020·Nature·Jian ShangFang Li
Apr 8, 2020·Emerging Infectious Diseases·Steven SancheRuian Ke
Mar 5, 2020·BioRxiv : the Preprint Server for Biology·Chuang LiuLei Liu

❮ Previous
Next ❯

Citations

Jul 22, 2020·Journal of Medical Virology·Laura Torre-FuentesJordi A Matías-Guiu
Jul 17, 2020·Acta Physiologica·Giada PontecorviAlessandra Carè
Jul 1, 2020·Clinical Chemistry and Laboratory Medicine : CCLM·Giuseppe LippiFabian Sanchis-Gomar
Aug 11, 2020·Médecine sciences : M/S·Erwan SallardÉtienne Decroly
Aug 14, 2020·The FEBS Journal·Yousef TizabiMichael Aschner
Jul 10, 2020·Journal of Virology·Xuesen ZhaoJu-Tao Guo
Jul 15, 2020·Journal of Virology·Xuesen ZhaoHanxin Lin
Sep 3, 2020·Nanomedicine·Georgia Wilson JonesBengt Fadeel
Sep 5, 2020·Seminars in Liver Disease·Maria J Lizardo-ThiebaudNalu Navarro-Alvarez
Sep 10, 2020·JAMA : the Journal of the American Medical Association·Gregory CurfmanPhilip Greenland
Sep 10, 2020·PloS One·Lluc Farrera-SolerNicolas Winssinger
Jul 15, 2020·The Journal of Biological Chemistry·Ella HartenianBritt A Glaunsinger
Sep 18, 2020·Journal of Biomolecular Structure & Dynamics·Janmejaya RoutUmakanta Tripathy
Sep 23, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Shari B BrosnahanDavid A Kaufman
Sep 24, 2020·Reviews in Medical Virology·Sakthivel SuganyaMadasamy Parani
Sep 10, 2020·Hepatology Communications·Yuval IshayYaron Ilan
Aug 18, 2020·Transboundary and Emerging Diseases·Guangzhi ZhangShangjin Cui
Sep 30, 2020·Molecular Neurobiology·Dmitri BougakovElkhonon Goldberg
Sep 29, 2020·African Journal of Urology : the Official Journal of the Pan African Urological Surgeons' Association (PAUSA)·Jeff John, Ken Kesner
Jul 18, 2020·The Journal of Biological Chemistry·Ce ZhangQingyu Wu
Aug 2, 2020·Journal of Translational Medicine·Darawan RinchaiDamien Chaussabel
Jul 29, 2020·International Journal of Molecular Sciences·Rami A Al-HoraniKholoud F Aliter
Jul 29, 2020·Frontiers in Physiology·Francisco J Barrantes
Aug 25, 2020·SN Comprehensive Clinical Medicine·Yi Ming, Liu Qiang
Aug 8, 2020·Genes and Immunity·Lourdes Ortiz-Fernández, Amr H Sawalha
Sep 20, 2020·International Journal of Molecular Sciences·Arun Samidurai, Anindita Das
Aug 19, 2020·International Journal of Molecular Sciences·Andreas RitterJuping Yuan
Aug 21, 2020·Journal of Cellular and Molecular Medicine·John T MooreDeepak Kumar
Sep 13, 2020·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Rami A Al-Horani
Jul 28, 2020·DNA and Cell Biology·Arghavan AsghariNegin Parsamanesh
Aug 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Stefania MazziniRoberto Artali
Sep 6, 2020·Nature Communications·Leo HankeGerald M McInerney
Sep 12, 2020·Cells·Pasquale CampanaAdriana Borriello
Jun 2, 2020·Infection & chemotherapy·Hyoung Shik Shin

❮ Previous
Next ❯

Datasets Mentioned

BETA
MG916901.1
QHD43416.1
AFR58740.1
AFS88936.1

Methods Mentioned

BETA
pull-down
surface plasmon resonance
flow cytometry
gel filtration
Assay
transfection
immunoprecipitation

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Epigenetics Insights from Twin Studies

Find the latest research on epigenetics and twin studies here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.