An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo
Moriya Tsuji, Manoj S. Nair, Kazuya Masuda, Candace Castagna, Zhenlu Chong, Tamarand L. Darling, Kuljeet Seehra, Youngmin Hwang, Ágata Lopes Ribeiro, Geovane Marques Ferreira, Laura Corredor, Jordana Grazziela Alves Coelho-dos-Reis, Yukiko Tsuji, Munemasa Mori, Adrianus C. M. Boon, Michael Diamond, Yaoxing Huang, David D. Ho
Abstract
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 infections 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-[Formula: see text]. A chemical compound 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.