The OM-85 Bacterial Lysate Inhibits SARS-CoV-2 Infection of Epithelial Cells by Downregulating SARS-CoV-2 Receptor Expression
American Journal of Respiratory and Critical Care Medicine
; 205(1), 2022.
Article
in English
| EMBASE | ID: covidwho-1927798
ABSTRACT
RATIONALE Treatments for the coronavirus disease of 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through the interactions of its spike (S) protein with ACE2 and TMPRSS2 on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells. OM-85, a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile, is widely used to prevent recurrent respiratory infections. Our finding that the airway administration of OM-85 inhibits Ace2 and Tmprss2 transcription in mouse lungs prompted us to investigate whether and how OM-85 may protect non-human primate and human epithelial cells against SARS-CoV-2 infection. METHODS:
ACE2 and TMPRSS2 mRNA and protein expression, cell binding of SARS-CoV-2 S1 protein, cell entry of SARS-CoV-2 S protein-pseudotyped lentiviral particles, and SARS-CoV-2 cell infection were measured in kidney, lung and intestinal epithelial cell lines, primary human bronchial epithelial cells, and ACE2- transfected HEK293T cells treated with OM-85 in vitro.RESULTS:
OM-85 significantly downregulated ACE2 and TMPRSS2 mRNA in epithelial cell lines and primary bronchial epithelial cells, and strongly inhibited SARS-CoV-2 S protein binding to, SARS-CoV-2 S proteinpseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on the downregulation of SARS-CoV-2 receptor expression.CONCLUSIONS:
OM-85 inhibits SARS-CoV-2 epithelial cell infection in vitro by downregulating SARS-CoV-2 receptor expression. Further studies are warranted to assess whether OM-85 may prevent and/or reduce the severity of COVID-19.
angiotensin converting enzyme 2; bacterium lysate; endogenous compound; messenger RNA; transmembrane protease serine 2; animal cell; animal experiment; bronchiole cell; conference abstract; controlled study; coronavirus disease 2019; down regulation; gene expression; genetic transcription; HBEC cell line (bronchial epithelium); HEK293T cell line; human; in vitro study; intestine epithelium cell; kidney cell culture; Lentivirus; male; mouse; nonhuman; prevention; primate; protein binding; protein expression; respiratory tract infection; Severe acute respiratory syndrome coronavirus 2
Full text:
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
American Journal of Respiratory and Critical Care Medicine
Year:
2022
Document Type:
Article
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