UMMS Affiliation

Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine; Program in Molecular Medicine; Department of Pathology

Publication Date

2021-05-18

Document Type

Article

Disciplines

Hemic and Immune Systems | Immunology of Infectious Disease | Immunopathology | Immunoprophylaxis and Therapy | Infectious Disease | Microbiology | Virus Diseases

Abstract

Coronaviruses are a family of RNA viruses that cause acute and chronic diseases of the upper and lower respiratory tract in humans and other animals. SARS-CoV-2 is a recently emerged coronavirus that has led to a global pandemic causing a severe respiratory disease known as COVID-19 with significant morbidity and mortality worldwide. The development of antiviral therapeutics are urgently needed while vaccine programs roll out worldwide. Here we describe a diamidobenzimidazole compound, diABZI-4, that activates STING and is highly effective in limiting SARS-CoV-2 replication in cells and animals. diABZI-4 inhibited SARS-CoV-2 replication in lung epithelial cells. Administration of diABZI-4 intranasally before or even after virus infection conferred complete protection from severe respiratory disease in K18-ACE2-transgenic mice infected with SARS-CoV-2. Intranasal delivery of diABZI-4 induced a rapid short-lived activation of STING, leading to transient proinflammatory cytokine production and lymphocyte activation in the lung associated with inhibition of viral replication. Our study supports the use of diABZI-4 as a host-directed therapy which mobilizes antiviral defenses for the treatment and prevention of COVID-19.

Keywords

SARS-CoV-2, coronavirus, COVID-19, antiviral therapeutics, diamidobenzimidazole compound, diABZI-4, STING, SARS-CoV-2 replication

Rights and Permissions

Copyright © 2021, American Association for the Advancement of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

DOI of Published Version

10.1126/sciimmunol.abi9002

Source

Humphries F, Shmuel-Galia L, Jiang Z, Wilson R, Landis P, Ng SL, Parsi KM, Maehr R, Cruz J, Morales-Ramos A, Ramanjulu JM, Bertin J, Pesiridis GS, Fitzgerald KA. A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection. Sci Immunol. 2021 May 18;6(59):eabi9002. doi: 10.1126/sciimmunol.abi9002. PMID: 34010139; PMCID: PMC8158975. Link to article on publisher's site

Journal/Book/Conference Title

Science immunology

Related Resources

Link to Article in PubMed

PubMed ID

34010139

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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