Abstract
Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Angiotensin-Converting Enzyme 2
- Antibodies, Viral / immunology*
- Betacoronavirus / chemistry
- Betacoronavirus / immunology
- Betacoronavirus / physiology*
- Broadly Neutralizing Antibodies / immunology*
- COVID-19
- Calcium Channels / metabolism
- Cathepsin L / metabolism
- Cathepsins / antagonists & inhibitors
- Cathepsins / metabolism
- Cell Fusion
- Coronavirus Infections / immunology
- Cross Reactions
- Endocytosis
- Giant Cells / physiology
- HEK293 Cells
- Humans
- Neutralization Tests
- Pandemics
- Peptidyl-Dipeptidase A / metabolism
- Phosphatidylinositol 3-Kinases / metabolism
- Pneumonia, Viral / immunology
- Protein Domains
- Protein Multimerization
- Receptors, Virus / metabolism
- SARS-CoV-2
- Severe Acute Respiratory Syndrome / immunology
- Severe acute respiratory syndrome-related coronavirus / immunology
- Spike Glycoprotein, Coronavirus / chemistry
- Spike Glycoprotein, Coronavirus / immunology*
- Spike Glycoprotein, Coronavirus / metabolism*
- Trypsin / metabolism
- Virus Internalization*
Substances
- Antibodies, Viral
- Broadly Neutralizing Antibodies
- Calcium Channels
- Receptors, Virus
- Spike Glycoprotein, Coronavirus
- TPCN2 protein, human
- spike glycoprotein, SARS-CoV
- spike protein, SARS-CoV-2
- PIKFYVE protein, human
- Cathepsins
- Peptidyl-Dipeptidase A
- ACE2 protein, human
- Angiotensin-Converting Enzyme 2
- Trypsin
- Cathepsin L