An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo

Prophylactic vaccines for SARS-CoV-2 have lowered the incidence of severe COVID-19, but emergence of viral variants that are antigenically distinct from the vaccine strains are of concern and additional, broadly acting preventive approaches are desirable. Here, we report on a glycolipid termed 7DW8-5 that exploits the host innate immune system to enable rapid control of viral infec-tions in vivo. This glycolipid binds to CD1d on antigen-presenting cells and thereby stimulates NKT cells to release a cascade of cytokines and chemokines. The intranasal administration of 7DW8-5 prior to virus exposure significantly blocked infection by three different authentic variants of SARS-CoV-2, as well as by respiratory syncytial virus and influenza virus, in mice or hamsters. We also found that this protective antiviral effect is both host-directed and mechanism-specific, requiring both the CD1d molecule and interferon-?. A chemical com-pound like 7DW8-5 that is easy to administer and cheap to manufacture may be useful not only in slowing the spread of COVID-19 but also in responding to future pandemics long before vaccines or drugs are developed.

Automated summary

A glycolipid called 7DW8-5 has been found to stimulate NKT cells to release cytokines and chemokines, enabling rapid control of viral infections. Intranasal administration of 7DW8-5 effectively blocked infections by various variants of SARS-CoV-2, respiratory syncytial virus, and influenza virus. This glycolipid could be a useful tool in preventing virus spread and responding to future pandemics.