An RNA molecule that stimulates the body’s early antiviral defence system may provide protection against a range of SARS-CoV-2 variants, including Delta, according to a study conducted in mice. Ribonucleic acid (RNA) is a single stranded molecule essential in various biological roles and expression of genes.
Researchers at Yale School of Medicine in the US noted that the molecule could lead to new treatments for COVID-19 in immunocompromised patients. The research, published recently in the Journal of Experimental Medicine (JEM), could also provide an inexpensive therapeutic option for many developing countries that currently lack access to vaccines. The study was conducted before Omicron was identified and did not test for the variant which is behind the current spike in COVID-19 cases in many countries.
The researchers noted that the vaccines against SARS-CoV-2 are highly effective at preventing severe disease and death. However, vaccine availability is extremely limited in many low-income countries, and vaccine-resistant strains of the virus are also emerging, they said.
“This is why, in addition to the use of vaccines in preventing COVID-19, efforts are required to develop efficacious therapeutics against SARS-CoV-2," said Akiko Iwasaki, a professor at Yale School of Medicine. The body’s first line of defence against SARS-CoV-2 — before the involvement of antibodies and T cells — is thought to depend on receptor molecules such as RIG-I.
These molecules recognise the virus’s genetic material and induce the production of signalling proteins known as type I interferons. These interferons promote the production of proteins that can inhibit viral reproduction and stimulate the recruitment of immune cells to fight the infection, the researchers said.
Multiple studies have suggested that early and robust production of interferons protects against COVID-19, whereas delayed production is associated with severe disease. A clinical trial has shown that treating COVID-19 patients with purified interferon protein early during disease can reduce mortality, but manufacturing interferons is extremely expensive.
The latest study suggests a cheaper option in the form of short RNA molecules that mimic SARS-CoV-2’s genetic material and activate the RIG-I receptor to stimulate production of type I interferons by the body’s own cells. The researchers tested their approach in mice susceptible to SARS-CoV-2 infection.
A single dose of an RNA molecule named SLR14 was sufficient to protect the mice from severe disease and death, particularly if the treatment was provided shortly before or soon after exposure to the virus, the researchers said.
When administered shortly after viral infection, SLR14 was more effective than treating mice with purified interferon protein, they said. SLR14 protected mice from all emerging SARS-CoV-2 variants, including Delta.
The researchers tested SLR14 in immunocompromised mice chronically infected with SARS-CoV-2. The RNA molecule was able to completely clear the virus from these animals, even though they lack both T cells and antibody-producing B cells.
The researchers noted that RNA molecules like SLR14 are relatively cheap and easy to manufacture. “SLR14 therefore holds great promise as a new class of RNA therapeutics that can be applied as antivirals against SARS-CoV-2, Iwasaki added.