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- Title
An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo.
- Authors
Tsuji, Moriya; Nair, Manoj S.; Masuda, Kazuya; Castagna, Candace; Chong, Zhenlu; Darling, Tamarand L.; Seehra, Kuljeet; Hwang, Youngmin; Ribeiro, Ágata Lopes; Ferreira, Geovane Marques; Corredor, Laura; Coelho-dos-Reis, Jordana Grazziela Alves; Tsuji, Yukiko; Mori, Munemasa; Boon, Adrianus C. M.; Diamond, Michael S.; Huang, Yaoxing; Ho, David D.
- 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- γ . 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. 7DW8-5 is a glycolipid that binds CD1d and stimulates invariant natural killer T (iNKT) cells. Here the authors show that 7DW8-5, when administered intranasally, provides prophylactic anti-viral effects against influenza, RSV, and SARS-CoV-2 in mice or hamsters, and that this effect is mediated by iNKT cells and IFN-γ.
- Subjects
COVID-19; RESPIRATORY syncytial virus; VIRUS diseases; INFLUENZA; COVID-19 pandemic; SARS-CoV-2
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-39738-1