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.
Keywords: ACE2; COVID-19; SARS-CoV-2; TMPRSS2; coronavirus; entry; neutralization; priming; spike.
Copyright © 2020 Elsevier Inc. All rights reserved.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Ammonium Chloride / pharmacology
- Angiotensin-Converting Enzyme 2
- Animals
- Antibodies, Neutralizing / immunology
- Antibodies, Viral / immunology
- Betacoronavirus / chemistry
- Betacoronavirus / genetics
- Betacoronavirus / metabolism*
- COVID-19
- COVID-19 Serotherapy
- Cell Line
- Coronavirus / chemistry
- Coronavirus / genetics
- Coronavirus / physiology
- Coronavirus Infections / drug therapy*
- Coronavirus Infections / immunology
- Coronavirus Infections / therapy
- Drug Development
- Esters
- Gabexate / analogs & derivatives
- Gabexate / pharmacology
- Guanidines
- Humans
- Immunization, Passive
- Leucine / analogs & derivatives
- Leucine / pharmacology
- Pandemics
- Peptidyl-Dipeptidase A / chemistry
- Peptidyl-Dipeptidase A / metabolism*
- Pneumonia, Viral / drug therapy*
- Protease Inhibitors / pharmacology*
- Receptors, Virus / chemistry
- Receptors, Virus / metabolism
- SARS-CoV-2
- Serine Endopeptidases / metabolism*
- Severe acute respiratory syndrome-related coronavirus / physiology
- Spike Glycoprotein, Coronavirus / chemistry
- Spike Glycoprotein, Coronavirus / genetics
- Spike Glycoprotein, Coronavirus / metabolism*
- Vesiculovirus / genetics
- Virus Internalization / drug effects*
Substances
- (3-ethoxycarbonyloxirane-2-carbonyl)leucine (3-methylbutyl) amide
- Antibodies, Neutralizing
- Antibodies, Viral
- Esters
- Guanidines
- Protease Inhibitors
- Receptors, Virus
- Spike Glycoprotein, Coronavirus
- spike glycoprotein, SARS-CoV
- Ammonium Chloride
- camostat
- Gabexate
- Peptidyl-Dipeptidase A
- ACE2 protein, human
- Angiotensin-Converting Enzyme 2
- Serine Endopeptidases
- TMPRSS2 protein, human
- Leucine