A natural beta interferon-inducing therapeutic glycolipid from the microbiome that prevents and treats severe viral infection

One important clinical aspect of the current COVID-19 pandemic, as well as in influenza infection, is the wide variety of clinical presentations. Infections with either virus can lead to a clinical course that is anywhere on a spectrum from asymptomatic nasopharyngeal carriage to rapidly progressive fatal systemic disease. It has been shown that an important regulator of viral disease severity is host interferon beta (IFNβ) which is a crucial mediator of antiviral immunity and homeostatic immunoregulation. Our work has found that host natural IFNβ is regulated by the microbiome and specifically by glycolipids present on the surface of microbes from the phylum Bacteroides. We discovered that the critical Bacteroides molecule responsible for IFNβ induction is the outer membrane-associated lipooligosaccharide (LOS). LOS molecules regulate the IFNβ response both locally and systemically through induction in colonic dendritic cells and we have identified the molecular mechanism by which this occurs. The LOS of Bacteroides exists naturally in multiple structural variations. Our goal in this proposal is to identify a specific structural analog of the numerous glycolipid structures belonging to the lipooligosaccharides(LOS) of the Bacteroides phylum. Once we purify a specific IFNβ inducing structure, we will test it for prophylaxis and therapy in models of influenza and COVID-19 infection. Since these structures can be synthesized, our approach presents an exciting opportunity to develop a low-cost approach to minimizing severity of viral diseases as well as other diseases for which type 1 interferons can be used therapeutically.