An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo.
Moriya TsujiManoj S NairKazuya MasudaCandace CastagnaZhenlu ChongTamarand L DarlingKuljeet SeehraYoungmin HwangÁgata Lopes RibeiroGeovane Marques FerreiraLaura CorredorJordana Grazziela Alves Coelho-Dos-ReisYukiko TsujiMunemasa MoriAdrianus C M BoonMichael S. DiamondYaoxing HuangDavid D HoPublished in: Nature communications (2023)
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.
Keyphrases
- sars cov
- respiratory syncytial virus
- induced apoptosis
- respiratory syndrome coronavirus
- cell cycle arrest
- immune response
- copy number
- escherichia coli
- coronavirus disease
- cell death
- oxidative stress
- type diabetes
- preterm infants
- early onset
- gene expression
- cell proliferation
- metabolic syndrome
- adipose tissue
- respiratory tract
- skeletal muscle
- sensitive detection
- preterm birth