TY - JOUR
T1 - An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo
AU - Tsuji, Moriya
AU - Nair, Manoj S.
AU - Masuda, Kazuya
AU - Castagna, Candace
AU - Chong, Zhenlu
AU - Darling, Tamarand L.
AU - Seehra, Kuljeet
AU - Hwang, Youngmin
AU - Ribeiro, Ágata Lopes
AU - Ferreira, Geovane Marques
AU - Corredor, Laura
AU - Coelho-dos-Reis, Jordana Grazziela Alves
AU - Tsuji, Yukiko
AU - Mori, Munemasa
AU - Boon, Adrianus C.M.
AU - Diamond, Michael S.
AU - Huang, Yaoxing
AU - Ho, David D.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85164182797&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-39738-1
DO - 10.1038/s41467-023-39738-1
M3 - Article
C2 - 37402814
AN - SCOPUS:85164182797
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3959
ER -