A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection.
Sci Immunol
; 6(59)2021 05 18.
Article
in English
| MEDLINE | ID: covidwho-1234280
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Benzimidazoles
/
SARS-CoV-2
/
COVID-19
/
COVID-19 Drug Treatment
/
Membrane Proteins
Type of study:
Experimental Studies
Topics:
Vaccines
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Year:
2021
Document Type:
Article
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