Treatments for coronavirus disease 2019, 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 interactions of its spike (S) protein with angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (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. We found that airway OM-85 administration inhibits Ace2 and Tmprss2 transcription in the mouse lung, suggesting that OM-85 might hinder SARS-CoV-2/host cell interactions.
Objectives
We sought to investigate whether and how OM-85 treatment protects nonhuman primate and human epithelial cells against SARS-CoV-2.
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 transcription and surface ACE2 protein expression in epithelial cell lines and primary bronchial epithelial cells. OM-85 also strongly inhibited SARS-CoV-2 S1 protein binding to, SARS-CoV-2 S protein–pseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on SARS-CoV-2 receptor downregulation.
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 coronavirus disease 2019.
This work was funded in part by a research grant provided by OM Pharma SA to the University of Arizona. Support was also provided by postdoctoral NIH fellowships from T32 ES007091 and the BIO5 Institute (to A.D.V.), a predoctoral T32 HL007249 fellowship (to S.R.V.L.), and P01AI148104, R21AI144722, and R25HL126140 (to D.V.).
Disclosure of potential conflict of interest: D. Vercelli and V. Pivniouk are inventors in PCT/EP2019/074562, “Method of Treating and/or Preventing Asthma, Asthma Exacerbations, Allergic Asthma and/or Associated Conditions with Microbiota Related to Respiratory Disorders.” M. Kraft has received grants from the National Institutes of Health, the American Lung Association, Chiesi, Sanofi, and Astra-Zeneca, speaker fees from Chiesi outside this work, and consulting fees from Astra-Zeneca and Sanofi, outside the submitted work. J. Nikolich-Zugich is cochair of the Scientific Advisory Board of and receives research funding from Young Blood Institute, Inc. The rest of the authors declare that they have no relevant conflicts of interest.
