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.

Details

Title
An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo
Author
Tsuji, Moriya 1   VIAFID ORCID Logo  ; Nair, Manoj S. 1   VIAFID ORCID Logo  ; Masuda, Kazuya 1   VIAFID ORCID Logo  ; Castagna, Candace 2 ; Chong, Zhenlu 3 ; Darling, Tamarand L. 3 ; Seehra, Kuljeet 3 ; Hwang, Youngmin 4 ; Ribeiro, Ágata Lopes 5 ; Ferreira, Geovane Marques 5 ; Corredor, Laura 2 ; Coelho-dos-Reis, Jordana Grazziela Alves 5 ; Tsuji, Yukiko 6 ; Mori, Munemasa 4 ; Boon, Adrianus C. M. 7   VIAFID ORCID Logo  ; Diamond, Michael S. 8   VIAFID ORCID Logo  ; Huang, Yaoxing 1   VIAFID ORCID Logo  ; Ho, David D. 9   VIAFID ORCID Logo 

 Columbia University Irving Medical Center, Aaron Diamond AIDS Research Center, New York, USA (GRID:grid.239585.0) (ISNI:0000 0001 2285 2675); Columbia University Irving Medical Center, Division of Infectious Diseases, Department of Medicine, New York, USA (GRID:grid.239585.0) (ISNI:0000 0001 2285 2675) 
 Columbia University Irving Medical Center, Institute of Comparative Medicine, New York, USA (GRID:grid.239585.0) (ISNI:0000 0001 2285 2675) 
 Washington University School of Medicine, Department of Medicine, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002) 
 Columbia University Irving Medical Center, Columbia Center for Human Development, Pulmonary Allergy & Critical Care Medicine, Department of Medicine, New York, USA (GRID:grid.239585.0) (ISNI:0000 0001 2285 2675) 
 Federal University of Minas Gerais, Basic and Applied Virology Laboratory, Department of Microbiology, Belo Horizonte, Brazil (GRID:grid.8430.f) (ISNI:0000 0001 2181 4888) 
 Columbia University Irving Medical Center, Aaron Diamond AIDS Research Center, New York, USA (GRID:grid.239585.0) (ISNI:0000 0001 2285 2675) 
 Washington University School of Medicine, Department of Medicine, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002); Washington University School of Medicine, Department of Molecular Microbiology, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002); Washington University School of Medicine, Department of Pathology and Immunology, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002) 
 Washington University School of Medicine, Department of Medicine, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002); Washington University School of Medicine, Department of Molecular Microbiology, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002); Washington University School of Medicine, Department of Pathology and Immunology, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002); Washington University School of Medicine, The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002) 
 Columbia University Irving Medical Center, Aaron Diamond AIDS Research Center, New York, USA (GRID:grid.239585.0) (ISNI:0000 0001 2285 2675); Columbia University Irving Medical Center, Division of Infectious Diseases, Department of Medicine, New York, USA (GRID:grid.239585.0) (ISNI:0000 0001 2285 2675); Columbia University Vagelos College of Physicians and Surgeons, Department of Microbiology and Immunology, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
Pages
3959
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2832906412
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.