A simple RNA molecule boosts the immune system’s “first responders” to viral infection and may even wipe out SARS-CoV-2 virus in mice with chronic cases of COVID-19, a new study from Yale School of Medicine finds.
The molecule, known as SLR14, is a simple, easy-to-make loop of RNA that can trigger the production of interferons, a group of proteins produced by immune cells that are key to the body’s innate or initial response to infection. Multiple studies have shown that COVID-19 patients who produce high levels of interferons have much better outcomes than those whose interferon levels are low during the early days of infection.
Treated mice also responded well to numerous variants of SARS-CoV-2, the virus that causes COVID-19, including the Delta variant, currently the predominant strain of the virus in the United States, according to the new report published Nov. 10 in the journal Experimental Medicine.
If clinical trials in humans confirm the efficacy of SLR14, the relatively inexpensive compound could help reduce COVID-19 cases in low-income countries where vaccine availability is limited, the researchers say. It may also provide important benefits for immunocompromised individuals who are unable to create sufficient levels of antibody-producing B cells and virucidal T cells.
“SLR14 therefore holds great promise as a new class of RNA therapeutics that can be used as antiviral agents against SARS-CoV-2,” said Akiko Iwasaki, the Waldemar Von Zedtwitz Professor of Immunology and Molecular, Cellular and Developmental Biology at Yale and corresponding author of the paper. “In addition, because this RNA-based therapeutic approach is simple and versatile, our study will facilitate pandemic preparedness and response to future respiratory pathogens sensitive to Type I interferons.”
Typically, vaccines, such as those that fight COVID-19, introduce harmless elements of the virus to trigger production of T and B cells by the body’s adaptive immune system, which can recognize previous pathogens and mount a targeted response. Treatments such as monoclonal antibodies are also designed to mimic this immune response at a later stage.
For the new study, a team led by first author Tianyang Mao, a graduate student in Iwasaki’s lab, examined whether compounds such as SLR14 could activate the innate immune system and protect against viral infections, including COVID-19.
In experiments, the researchers found that a single dose of the compound was enough to protect mice from severe illness and death, worked against a variety of variants, and could even eradicate the virus from mice with chronic infections.
“The results of innate immune activation clearing chronic infections were surprising and spectacular,” Iwasaki said.
Patent rights to SLR14 and similar compounds are owned by RIGimmune – a company co-founded by Iwasaki and Anna Pyle, Sterling Professor of Molecular, Cellular and Developmental Biology at Yale and a co-author of this study – which is seeking novel agents which can fights various pathogens.