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.
Associated Clinical Trials
Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins
Localization of neutralizing epitopes and the receptor-binding site within the amino-terminal 330 amino acids of the murine coronavirus spike protein
Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China
The mammalian phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates endosome-to-TGN retrograde transport
Efficient multiplication of human metapneumovirus in Vero cells expressing the transmembrane serine protease TMPRSS2.
Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites.
Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2
Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response
Cleavage and activation of the severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-like protease.
The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies
TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium
Middle East respiratory syndrome coronavirus infection mediated by the transmembrane serine protease TMPRSS2
Role of the spike glycoprotein of human Middle East respiratory syndrome coronavirus (MERS-CoV) in virus entry and syncytia formation
Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein
Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment
Human Coronavirus HKU1 Spike Protein Uses O-Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme
Identification of the Receptor-Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1
The phosphatidylinositol-3-phosphate 5-kinase inhibitor apilimod blocks filoviral entry and infection.
Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1
Identification of H209 as Essential for pH 8-Triggered Receptor-Independent Syncytium Formation by S Protein of Mouse Hepatitis Virus A59
NAADP-dependent Ca2+ signaling regulates Middle East respiratory syndrome-coronavirus pseudovirus translocation through the endolysosomal system
Human coronaviruses OC43 and HKU1 bind to 9-O -acetylated sialic acids via a conserved receptor-binding site in spike protein domain A
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Currently available intravenous immunoglobulin contains antibodies reacting against severe acute respiratory syndrome coronavirus 2 antigens
Protocol and Reagents for Pseudotyping Lentiviral Particles with SARS-CoV-2 Spike Protein for Neutralization Assays.
The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications
Potential differential effects of renin-angiotensin system inhibitors on SARS-CoV-2 infection and lung injury in COVID-19
Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies.
Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening.
Broad-Spectrum Coronavirus Fusion Inhibitors to Combat COVID-19 and Other Emerging Coronavirus Diseases
Targeting SARS-CoV-2 receptors as a means for reducing infectivity and improving antiviral and immune response: an algorithm-based method for overcoming resistance to antiviral agents.
The mechanism and energetics of a ligand-controlled hydrophobic gate in a mammalian two pore channel
Evolutionary relationships and sequence-structure determinants in human SARS coronavirus-2 spike proteins for host receptor recognition
Characteristics and serological patterns of COVID-19 convalescent plasma donors: optimal donors and timing of donation
Revisiting potential druggable targets against SARS-CoV-2 and repurposing therapeutics under preclinical study and clinical trials: A comprehensive review
Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review
Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection via Endocytosis or Macropinocytosis
Comprehensive analysis of drugs to treat SARS‑CoV‑2 infection: Mechanistic insights into current COVID‑19 therapies (Review)
Evidence supporting the use of peptides and peptidomimetics as potential SARS-CoV-2 (COVID-19) therapeutics
Neutralizing and cross-reacting antibodies: implications for immunotherapy and SARS-CoV-2 vaccine development.
The renin-angiotensin-aldosterone system: Role in pathogenesis and potential therapeutic target in COVID-19.
Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: an in silico study for drug development.
Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19
Antibody-based immunotherapeutics and use of convalescent plasma to counter COVID-19: advances and prospects
A diagnostic genomic signal processing (GSP)-based system for automatic feature analysis and detection of COVID-19.
Severe acute respiratory syndrome coronavirus 2 may be an underappreciated pathogen of the central nervous system
A novel biparatopic hybrid antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy.
SARS-CoV-2 Infections and ACE2: Clinical Outcomes Linked With Increased Morbidity and Mortality in Individuals With Diabetes.
This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.