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1.
Sci Immunol ; 5(47)2020 05 13.
Article in English | MEDLINE | ID: covidwho-260039

ABSTRACT

Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA are frequently observed in COVID-19 patients. However, it is unclear whether SARS-CoV-2 replicates in the human intestine and contributes to possible fecal-oral transmission. Here, we report productive infection of SARS-CoV-2 in ACE2+ mature enterocytes in human small intestinal enteroids. Expression of two mucosa-specific serine proteases, TMPRSS2 and TMPRSS4, facilitated SARS-CoV-2 spike fusogenic activity and promoted virus entry into host cells. We also demonstrate that viruses released into the intestinal lumen were inactivated by simulated human colonic fluid, and infectious virus was not recovered from the stool specimens of COVID-19 patients. Our results highlight the intestine as a potential site of SARS-CoV-2 replication, which may contribute to local and systemic illness and overall disease progression.


Subject(s)
Betacoronavirus/physiology , Enterocytes/virology , Membrane Proteins/metabolism , Serine Endopeptidases/metabolism , Virus Internalization , Animals , Cell Line , Duodenum/cytology , Enterocytes/pathology , Humans , Mice , Organoids/virology , Peptidyl-Dipeptidase A/metabolism , Rotavirus/physiology , Vesiculovirus/genetics
2.
Cell ; 181(2): 271-280.e8, 2020 04 16.
Article in English | MEDLINE | ID: covidwho-4561

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.


Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections/drug therapy , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/drug therapy , Protease Inhibitors/pharmacology , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects , Ammonium Chloride/pharmacology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/chemistry , Betacoronavirus/genetics , Cell Line , Coronavirus/chemistry , Coronavirus/genetics , Coronavirus/physiology , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Drug Development , Gabexate/analogs & derivatives , Gabexate/pharmacology , Humans , Immunization, Passive , Leucine/analogs & derivatives , Leucine/pharmacology , Pandemics , Peptidyl-Dipeptidase A/chemistry , Receptors, Virus/chemistry , Receptors, Virus/metabolism , SARS Virus/physiology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Vesiculovirus/genetics
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