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

• Published in: Nature communications Vol. 14; no. 1; pp. 3959 - 12
• Main 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.07.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 14/105; 38/39; 631/250/2520; 631/250/255/2514; 631/326/596/2553; 64; 64/110; 64/60; 692/4017; 96/31; Antigen-presenting cells; Antigens; Antiviral agents; Antiviral drugs; CD1d antigen; Chemical compounds; Chemokines; COVID-19; COVID-19 vaccines; Hamsters; Humanities and Social Sciences; Immune system; Immunostimulation; Immunosuppressive agents; Influenza; Innate immunity; Intranasal administration; Lymphocytes T; multidisciplinary; Natural killer cells; Pandemics; Public health; Respiratory syncytial virus; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Vaccines; Viral diseases; Viral infections; Viruses; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-39738-1

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.