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

Nature communications 2023 Jul 05

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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. © 2023. The Author(s).

Citation

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 S Diamond, Yaoxing Huang, David D Ho. An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo. Nature communications. 2023 Jul 05;14(1):3959